Pediatric Allergy,Immunology,and Pulmonology

Respiratory viruses are known to cause asthma exacerbations. There have been no previous studies in children looking at which viruses have the greatest capacity to induce an asthma exacerbation. This study attempts to identify viruses with the most asthmagenic properties. The objective of this study is to determine the prevalence of viral infections in children with asthma exacerbations, and to correlate specific viral infections with clinical severity. Nasopharyngeal and oropharyngeal swabs were collected for viral culture from 101 asthma patients presenting to the Children's Hospital of Philadelphia Emergency Department with an asthma exacerbation. Patients ranged in age from 3 years to 18 years. One hundred and one well asthmatics were recruited from the Allergy Clinic and Department of Pediatrics to serve as control patients. Control patients were enrolled within 2 weeks of study patients, and were matched by age, gender, and ethnic group. Viral isolates were correlated with the age, gender, ethnic group, and for children with asthma exacerbations disposition. There was a statistically significant (Fisher's exact test p = 0.022) increase in culture-proven viral isolates in children with asthma exacerbations (14.9%), as compared with well asthmatic children (3.0%). Respiratory synctial virus was the most prevalent virus isolated, representing 46.7% [95%, Confidence interval (17.8, 69.3)] of all viral isolates. There also was a statistically significant increase in RSV isolates (p = 0.0269) from patients requiring pediatric intensive care compared with asthma patients with less severe exacerbations. Viral infections are common triggers of asthma exacerbations in children, and RSV is associated with the most severe exacerbations in children of all ages. Prevention, and/or treatment of RSV infection should be considered a high priority for the management of asthmatic children.

The object of this study is to determine whether celiac disease (CD) and atopic disorders are associated and whether atopy and gluten exposure are related. Ninety children (mean age of 9.3 years) being treated for CD were evaluated for a personal and family history of atopic diseases by a detailed questionnaire. In addition, study subjects had a peripheral blood eosinophil count, serum IgE, and skin prick tests for 10 common allergens. Ninety healthy children who attended pediatric well-child clinics or were admitted to the hospital for minor surgery served as age- and sex-matched controls. CD was excluded in the control group by clinical evaluation and by negative anti-gliadin (IgA and IgG) and anti-endomysium antibodies. In the children with CD, the age of onset of atopic disorders was compared with the age of diagnosis of CD. The prevalence of atopic disorders was compared in patients with CD who were submitted to gluten challenge or who had spontaneous challenges as teenagers by consuming gluten in their diet. No differences in the prevalence of atopic disorders was found in the group of children with CD compared to the healthy controls. The prevalence of atopic disorders did not increase with increasing age at diagnosis of CD and was not higher in children with CD who had gluten challenges. The conclusions were: CD and atopy are not associated in childhood celiac disease and atopic disorders are not related to gluten exposure.

Tumor necrosis factor receptors (TNF-R) are expressed on the cell membrane in asthma and soluble receptors are released into the extracellular space. The aim of the present study was to assess whether a correlation exists between bronchial hyperreactivity and the serum sTNF-R1 level in symptom-free, previously asthmatic adults and their offspring. Thirty-eight adults (suffered from bronchial asthma in childhood) and 43 children (offspring of asthmatic parents) were examined (mean age 35 and 15 years, respectively). Bronchial hyperreactivity was present in 21 adults and in 22 children, proved by stepwise methacholine (0.125, 0.25, 0.5%) airway challenge. Serum sTNF-R1 was determined by enzyme-linked immunoadsorbent assay (ELISA) method. Serum sTNF-R1 level was significantly higher in patients with bronchial hyperreactivity; all with hyperreactivity: 1.36 ± 0.29 ng/mL (mean ± SD, n = 43) versus without 1.20 ± 0.19 ng/mL (n = 38), p = 0.0065; children with hyperreactivity: 29 ± 0.26 ng/mL (n = 22) versus without 1.13 ± 0.11 ng/mL (n = 21), p = 0.0132; adults with hyperreactivity: 1.44 ± 0.31 ng/mL (n = 21) versus without 1.29 ± 0.24 ng/mL (n = 17), ns. In adults there was a significant negative correlation between serum sTNF-R1 level and the PD20 FVC of methacholine. In addition, a significant correlation was found between the sTNF-R1 level and the body mass index in adults. sTNF-R1 is elevated in hyperreactive patients. The activation of the TNF system might contribute to the pathogenesis of alteration of the respiratory system in bronchial hyper-reactivity.

Immune mechanisms are believed to contribute to the pathogenesis of bronchiolitis, but the nature of the critical pathways is unknown. The purpose of this study was to determine if quantities of the beta-chemokines macrophage inflammatory protein 1 alpha (MIP1α), eotaxin, and regulated on expression, normal T-cell expressed and secreted (RANTES) were different among infants with various forms of illness due to respiratory syncytial virus (RSV) infection. Samples of nasopharyngeal secretions (NPS) were obtained from 56 infants and children less than 13 months of age with either upper respiratory illness (URI) alone (n = 25) or lower respiratory tract illness (n = 31) due to RSV infection. Seventeen asymptomatic infants served as controls. Quantities of chemokines in secretions were compared between groups using the t-test after logarithmic transformation of data. Quantities of all three chemokines were increased at the time of RSV infection regardless of whether wheezing was present. However, concentrations of MIP-1α were significantly greater (p = 0.039) in wheezing infants than in those with URI alone. Quantities of MIP-1α (p = 0.029) and eotaxin (p = 0.017) were each significantly greater in wheezing infants with hypoxia than wheezing infants without hypoxia, and were inversely related to individual values of oxygen saturation. Finally, all three chemokines were still present at high levels in secretions for at least 2 to 3 weeks after respiratory symptoms had improved. These findings permit the hypothesis that MIP-1α may possibly play a role in the induction of inflammation and wheezing at the time of RSV infection.

One highly desirable objective of preventive medicine is to find predictive markers that could identify neonates who are at risk of developing atopic diseases. However, no one laboratory test is sufficiently sensitive and specific to be used for this purpose. The objective of this study was to evaluate the use of an in vitro IgE synthesis by cord blood lymphocytes of neonates with or without a family history of atopy. Cord blood mononuclear cells (CBMC) of 11 neonates with a family history of atopy and 9 neonates without a family history of atopy were incubated for 48 hr with human recombinant IL4 (hrIL4) in Petri plates. Cord blood lymphocytes (nonadherent cells) were then washed and incubated for an additional 9 days with various stimuli. hrIL4, hrIL4 + human recombinant interferon-gamma (hrIFNg), hrIL4 + anti-IL4 antibody (ab), hrIL-4 + antiCD40 ab, hrIL4 + anti-CD40 ab + betalactoglobulin (BLG) hrIL4 + anti-IFNg ab. Unstimulated cultures were included as negative controls. IgE concentrations in sera were measured by a fluorimmunoenzymatic method. Concentration of supernatants IgE ≥ 2.8 kU/L and serum IgE ≥ 0.7 kU/L were considered to be a positive test. Statistical analyses were performed using a Wilcoxon rank test, Mann-Whitney test for the sum of ranks, chi-square test, and/or Fisher's Exact test. Differences were considered significant when p < 0.05. The stimulatory effects of hr IL4 alone resulted in the highest production of IgE, which was significantly higher than the effects of hrIL4 + antiCD40 ab + BLG (medians: 2.9 vs 2.2 kU/L) or with hrIL4 + anti IL4 ab (medians: 2.9 vs. 2.4 kU/L) or the absence of any stimulus (medians of 2.9 vs. 0.5 kU/L). All stimuli resulted in production of Ig E, which was significantly higher than the IgE serum level alone (median of 0.17 kU/L). No significant differences were observed between the neonates with a family history of atopy versus those without a family history of atopy, neither with regard to median values of IgE nor with regard to the percentages of infants having IgE levels ≥ 2.8 kU/L in the culture's supernatants or ≥ 0.7 kU/L in the serum. Our results confirm that the neonatal B lymphocytes have the capacity to synthesize normal levels of IgE, if placed under adequate conditions. Low serum neonatal IgE levels are therefore the result of a deficit of the T-lymphocyte cooperation. However, in vitro IgE synthesis after exposure to a nonspecific stimulus (IL 4, anti-CD40 ab) is not a reliable predictive marker of atopy.