Next-generation reference interval for total IgE in the United States: A retrospective real-world analysis.

OBJECTIVE: To establish a next-generation reference interval (RI) for total IgE (tIgE) and evaluate its usefulness. METHODS: A new allergen-specific IgE (sIgE)-based tIgE RI, including a continuous RI in children, was established using the NHANES 2005-2006 project. The usefulness of the RI was evaluated by sensitivity (Sen), specificity (Spec), positive predictive value (PPV), negative predictive value (NPV), κ coefficient and consistency. RESULTS: The new tIgE RI showed better performance in identifying allergic sensitization (Sen 0.53, Spec 0.90, PPV 0.83, NPV 0.68, κ 0.44, consistency 0.72) than allergic diseases (Sen 0.37, Spec 0.75, PPV 0.55, NPV 0.60, κ 0.13, consistency 0.59). The 2014 U.S. tIgE RI was more effective in identifying allergic diseases (consistency 0.63 vs. 0.54, P<0.001) but less accurate in identifying allergic sensitization (consistency 0.59 vs. 0.67, P<0.001) in children than in adults. The new RI improved the accuracy of identifying allergic sensitization in children to a level similar to that in adults (consistency 0.72 vs 0.73, P=0.37) and maintained its advantage in identifying allergic diseases in children (consistency 0.64 vs 0.55, P<0.001). CONCLUSIONS: The established next-generation tIgE RI is useful for identifying allergic sensitization, especially in children.

Andrographolide sulfonate downregulation of TLR3-TRIF and amelioration of airway inflammation caused by respiratory syncytial virus infection.

Background: Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation. Methods: Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors (TLRs) 1-9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-ß (TRIF) were detected via Western blot analysis. Results: RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection. Conclusions: Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.

p53 suppresses the inflammatory response following respiratory syncytial virus infection by inhibiting TLR2.

-Respiratory syncytial virus (RSV) is a pivotal virus leading to acute lower respiratory tract infections in children under 5 years old. This study aimed to explore the correlation between p53 and Toll-like receptors (TLRs) post RSV infection. p53 levels exhibited a substantial decrease in nasopharyngeal aspirates (NPAs) from infants with RSV infection compared to control group. Manipulating p53 expression had no significant impact on RSV replication or interferon signaling pathway. Suppression of p53 expression led to heightened inflammation following RSV infection in A549 cells or airways of BALB/c mice. while stabilizing p53 expression using Nutlin-3a mitigated the inflammatory response in A549 cells. Additionally, Inhibiting p53 expression significantly increased Toll-like receptor 2 (TLR2) expression in RSV-infected epithelial cells and BALB/c mice. Furthermore, the TLR2 inhibitor, C29, effectively reduced inflammation mediated by p53 in A549 cells. Collectively, our results indicate that p53 modulates the inflammatory response after RSV infection through TLR2.

Age-related differences in IgE between childhood and adulthood allergic asthma: Analysis of NHANES 2005-2006.

Background: Asthma exhibits varying clinical features in children and adults. However, previous studies have mainly focused on the clinical significance of immunoglobulin E (IgE) in the diagnosis and treatment of asthma, disregarding the characteristics of IgE and its relevant factors. Objective: This study aimed to gain a better understanding of the differences in the characteristics of IgE between childhood and adulthood allergic asthma (AA). Methods: Patients with AA from the 2005 to 2006 National Health and Nutrition Examination Survey (NHANES) were divided into 3 groups based on their current age and onset age of AA: childhood AA (Group 1), childhood-onset adult AA (Group 2), and adulthood-onset AA (Group 3). Intragroup analysis and intergroup comparison were carried out, focusing on the characteristics and relevant factors of IgE, as well as the clinical relevance of total IgE (total IgE, tIgE) and allergen-specific IgE (allergen-specific IgE, sIgE). Results: A total of 424 patients were analyzed, including 187 with childhood AA, 132 with childhood-onset adult AA, and 105 with adulthood-onset AA. The concentration of tIgE was found to be higher in Group 1 (268.0, 118.0-686.0 kU/L) than in Group 2 (224.0, 78.0-494.0 kU/L) and Group 3 (165.0, 74.4-350.5 kU/L). The sensitization rates did not differ between Group 1 and Group 2 but were higher compared with Group 3, particularly for Alternaria-sIgE (50.3% and 46.2% vs 15.2%) and Aspergillus-sIgE (43.9% and 37.1% vs 16.2%). In Group 1, there was a negative correlation between pollen-sIgEs and indoor allergens, but this correlation was not commonly observed in Group 2 and Group 3. On the other hand, in Group 1, environmental chemicals such as phthalates, polyaromatic hydrocarbons, trihalomethanes, and phenols showed a positive correlation with IgE. However, a greater number of chemicals was observed in Group 2 and Group 3, including cotinine, metals, trihalomethanes, phthalates, phenols, and other volatile organic compounds (VOCs). Furthermore, in Group 1, IgE was positively correlated with asthma-related issues such as emergency visits, absenteeism, limited activities, and medication needs. These correlations were less common in Group 2 and Group 3, particularly in Group 3. Conclusions: There are notable differences in the characteristics and environmental factors of IgE among childhood AA, childhood-onset adult AA, and adulthood-onset AA. Additionally, IgE plays a more significant role in childhood AA due to its higher concentration, fewer relevant environmental chemicals and greater clinical relevance. This may partially explain the age-related features of asthma.