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.
Bronchiolitis/physiopathology/virology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Korea/epidemiology ; Male ; Metapneumovirus/pathogenicity ; Nasopharynx/virology ; Paramyxoviridae Infections/*epidemiology/*physiopathology/virology ; Respiratory Sounds/*physiopathology ; Respiratory Syncytial Virus Infections/*epidemiology/*physiopathology/virology ; Respiratory Syncytial Viruses/pathogenicity ; Retrospective Studies ; Seasons

OBJECTIVETo investigate the effects of different factors on the expressions of thymic stromal lymphopoietin (TSLP) in respiratory syncytial virus (RSV)-infected human airway epithelial cell line 16HBE cells.

METHODSRSV amplified by infecting Hep-2 cells was identified for its virulence. 16HBE cells were divided into six groups, namely the control group, RSV group, RSV/anti-TLR3 group, RSV/IFN-gamma group, RSV/IL-4 group and RSV/dexamethasone group with corresponding treatments. Real-time RT-PCR was used to examine the expression of TSLP mRNA in the cells 6 h after RSV infection. Western blotting was used to examine TSLP protein expression in the cells 24 h after the infection.

RESULTSThe expression of TSLP mRNA in 16HBE cells 6 h after RSV infection increased by 1.63-/+0.08 folds as compared to the expression level in the control cells. The expression of TSLP mRNA was significantly decreased in RSV-infected cells treated with anti-TLR3 antibody (P=0.034) and recombinant human IFN-gamma (P<0.001), but increased with the treatment by recombinant human IL-4 (P=0.025). Dexamethasone significantly inhibited the expression of TSLP mRNA in RSV-infected cells (P<0.001). The production of TSLP protein in 16HBE cells increased by 1.9 folds (P<0.001) 24 h after RSV infection, but underwent no significant changes after treatment with anti-TLR3 antibody (P=0.114). Recombinant human IFN-gamma significantly decreased while IL-4 enhanced the expression of TSLP protein in the infected cells (P=0.020 and 0.014, respectively). Dexamethasone significantly inhibited the increment of TSLP protein expression in RSV-infected cells (P<0.001).

CONCLUSIONSRSV infection can enhance the expressions of TSLP in human airway epithelial cells. IFN-gamma, anti-TLR3 and dexamethasone can inhibit the elevation of TSLP expression induced by RSV infection, but IL-4 synergistically enhances its expression.

Bronchi ; cytology ; metabolism ; Cell Line ; Cytokines ; genetics ; metabolism ; Epithelial Cells ; metabolism ; virology ; Humans ; Interferon-gamma ; pharmacology ; Interleukin-4 ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Respiratory Syncytial Virus Infections ; metabolism ; Respiratory Syncytial Viruses ; pathogenicity

OBJECTIVEIt is supposed that bronchial epithelial cells responses to the environmental stimuli are different between asthmatic and non-asthmatic individuals, which contribute to the pathogenesis of asthma. These different responses produce different mediators. If differential gene expressions are found in bronchial epithelial cells of asthmatic and non-asthmatic individuals after the same stimuli in vitro, and these genes are overexpressed in asthmatic children in vivo, then it is concluded that these genes may be associated with asthma. Therefore the authors analyzed the differential gene expressions in the bronchial epithelium cells of asthmatic and non-asthmatic children after RSV infection in vitro. Among these genes, Galectine-7 (lectin, galactoside-binding, soluble, 7, Galectin-7) was 8 times up-regulated in asthmatic children. Galectine-7 was associated with skin keratinocyte apoptosis. The authors hypothesized that Galectin-7 may also be associated with bronchial epithelial cell apoptosis in asthmatic children. The aim of this study was to understand the role of Galectine-7 in bronchial epithelial cell apoptosis in asthma.

METHODSThe bronchial mucosae of one asthmatic child and one non-asthmatic child were obtained by biopsy and cultured in vitro. The bronchial epithelial cells were infected by RSV. The differential gene expressions were analyzed with micro array. Among those differentially expressed genes, Galectin-7 was 8 times up-regulated in asthmatic children. The bronchial mucosae from 10 asthmatic children and 17 non-asthma children were investigated for cell DNA break, Galectine-7 and mRNA expression, Caspase-3 expression by TUNEL, hybridization in situ and immunochemistry. Image analysis was used for quantitative assessment.

RESULTSGalectine-7 gene was 8 times up-regulated in bronchial epithelial cells from asthmatic children after RSV infection in vitro. Galectin-7 and mRNA were overexpressed in bronchial epithelial cells in asthma in vivo. Bronchial epithelial cell apoptosis increased in asthma in vivo.

CONCLUSIONGalectin-7 may be associated with bronchial epithelial cell apoptosis in asthma.

Adolescent ; Apoptosis ; genetics ; Asthma ; metabolism ; pathology ; Biopsy ; Bronchi ; metabolism ; pathology ; Bronchoscopy ; Caspase 3 ; genetics ; metabolism ; Cells, Cultured ; Child ; Child, Preschool ; Epithelial Cells ; metabolism ; pathology ; virology ; Female ; Galectins ; genetics ; metabolism ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization ; In Situ Nick-End Labeling ; Infant ; Male ; RNA, Messenger ; Respiratory Mucosa ; cytology ; metabolism ; pathology ; virology ; Respiratory Syncytial Viruses ; pathogenicity ; Up-Regulation

OBJECTIVENeonatal Bacillus Calmette-Guerin (BCG) vaccination could decrease asthma prevalence in human according to "hygiene hypothesis". The authors proposed a hypothesis that effect of BCG vaccination on inhibiting asthma in human might be reversed by respiratory virus infection. The objective of this study was to observe combined effects of neonatal BCG vaccination and respiratory syncytial virus (RSV) infection on experimental asthma in mice.

METHODSNeonatal BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock-vaccinated at birth and mock-infected at 3 weeks of age. BCG + OVA group was BCG-vaccinated and mock-infected. RSV + OVA group was mock-vaccinated and RSV-infected. BCG + RSV + OVA group was BCG-vaccinated and RSV-infected. Except for control group, all the other groups underwent ovalbumin (OVA) sensitization and challenge. Airway responsiveness to inhaled methacholine was measured and bronchoalveolar lavage (BAL) was performed after the last challege. Cells in BAL fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lungs was scored by staining with hematoxylin and eosin.

RESULTS(1) The numbers of total white cells, lymphocytes, monocytes, neutrophils, and eosinophils in the BALF from all OVA-sensitized/challenged groups were significantly greater than those in control (P < 0.01), and BCG + OVA group had significantly lower total white cells, lymphocytes and eosinophils as compared with other OVA-sensitized/challenged groups (P < 0.05 or 0.01). (2) All OVA-sensitized/challenged groups had significantly lower IFNgamma (P < 0.05) and higher IL-4 (P < 0.05) level in BALF as compared with control, but there was no significant difference among all OVA sensitized/challenged groups. There was no significant difference in IL-10 level between all experimental groups. (3) All OVA-sensitized/challenged groups showed significantly higher serum OVA-specific IgE titers than control (P < 0.05 or 0.01), but no significant difference was found among all OVA sensitized/challenged groups. (4) RSV + OVA and BCG + RSV + OVA groups displayed the highest airway resistance and subsequently in order as follows: OVA group, BCG + OVA group and control group in severity of airway hyperreactivity (AHR), but no significant difference was found between RSV + OVA and BCG + RSV + OVA groups. (5) Histological score of peribronchiolitis, perivasculitis, alveolitis, and peribronchial eosinophilia in all OVA-sensitized/challenged groups was significantly higher than that in control. BCG + OVA group had significantly milder peribronchiolitis and peribronchial eosinophilia than the other OVA-sensitized/challenged groups (P < 0.05) and significantly milder alveolitis than OVA and BCG + RSV + OVA groups (P < 0.05).

CONCLUSIONNeonatal BCG vaccination decreased asthmatic inflammation and AHR and RSV infection could reverse anti-asthma effect of neonatal BCG vaccination in OVA-sensitized/challenged mouse model.

Animals ; Animals, Newborn ; Asthma ; immunology ; prevention & control ; BCG Vaccine ; administration & dosage ; immunology ; pharmacology ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; drug effects ; immunology ; secretion ; Immunoglobulin E ; analysis ; immunology ; Interferon-gamma ; analysis ; immunology ; Interleukin-10 ; analysis ; immunology ; Interleukin-4 ; analysis ; immunology ; Leukocytes ; drug effects ; immunology ; secretion ; Lung ; drug effects ; immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; administration & dosage ; immunology ; toxicity ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; immunology ; pathogenicity ; Treatment Outcome