Enmei Liu

The Polymorphism of IL-17 G-152A was Associated with Childhood Asthma and Bacterial Colonization of the Hypopharynx in Bronchiolitis

ObjectiveInterleukin (IL)-17 plays an important role in the pathogenesis of asthma. We investigated the association between single-nucleotide polymorphism (SNP) of IL-17 (rs2275913, IL-17 G-152A) and asthma-related traits. Its effect on IL-17 production was also attractive.MethodsOne hundred and sixty eight childhood asthmatic patients, 144 bronchiolitis patients, and 205 healthy controls were recruited in this study. SNP rs2275913 was genotyped by polymerase chain reaction–restriction fragment length polymorphism. Peripheral blood mononuclear cells (PBMCs) from parts of healthy controls with different genotype were isolated and cultured with phytohaemagglutinin (PHA) for detection of IL-17 in the supernatants.ResultsSNP rs2275913 was associated with asthma (P = 0.03) in genotype frequency test. Children with homozygous A were 2.29 times more likely to have asthma than others (95% confidence interval 1.39–3.78, P = 0.001). The strength of associations was moderately higher by allergy comorbidity. Furthermore, SNP rs2275913 A allele was associated with abnormal lung function and serum total IgE in asthmatics, although the production of IL-17 by PHA-induced PBMC seemed to be not different among individuals with different genotypes. The distribution of SNP rs2275913 in bronchiolitis was marginally statistically different with controls and demonstrated a tendency close to that in asthma. Higher Streptococcus pneumoniae and Moraxella catarrhalis detection rates were shown in bronchiolitis patients with homozygous A allele than those with other genotypes (20.8% vs. 3.7%, P < 0.01 and 20.8% vs. 6.2%, P = 0.03).ConclusionThe preliminary results demonstrate that IL-17 SNP rs2275913 was associated with several asthma-related traits and confers genetic susceptibility to childhood asthma. It may be used to develop markers to assess the risk of asthma, especially in the bronchiolitis population. It may be a potential bridge to connect the bacterial colonization and the onset of asthma.

Nebulized hypertonic saline/salbutamol solution treatment in hospitalized children with mild to moderate bronchiolitis

Background:  The objective of this study was to determine the efficacy and safety of nebulized 3% hypertonic saline solution and salbutamol in the treatment of mild to moderate bronchiolitis.

Genetic variability of respiratory syncytial viruses (RSV) prevalent in Southwestern China from 2006 to 2009: emergence of subgroup B and A RSV as dominant strains.

ABSTRACT Respiratory syncytial virus (RSV) is the most commonly identified viral agent in young children with acute respiratory tract infections (ARIs) and often causes repeated infections throughout life. This study investigated the genetic variability of the attachment (G) protein gene among RSV strains prevalent in southwestern China. Reverse transcription-PCR (RT-PCR) for a fragment of the RSV G gene was performed with nasopharyngeal aspirates (NPAs) collected from children with ARIs hospitalized in Chongqing Childrens Hospital, Chongqing, China. A total of 1,387 NPA specimens were collected from April 2006 to March 2009, and 439 (31.7%) were positive for RSV. During the study period, subgroup A and B viruses accounted for 79.5% (349/439) and 19.8% (87/439) of the total positive samples, respectively. Both subgroup A and B viruses were identified in three samples. Subgroup A viruses were predominant during two epidemic seasons (2006 to 2008), while subgroup B strains prevailed during the 2008-2009 epidemic season. Phylogenetic analyses showed that all 30 group A strains could be clustered into one genotype, genotype GA2, and 30 group B strains could be clustered into three genotypes, genotypes GB1, GB3, and BA, among which 17 genotype BA strains were detected from 23 group B strains selected during the 2008-2009 epidemic season. The G gene of genotype BA was predicted to encode proteins of five different lengths. These data suggest that group A RSV likely predominated in southwestern China and that a new genotype of subgroup B with a 60-nucleotide insertion, named BA-like virus, became the dominant genotype in the 2008-2009 epidemic season.

Resveratrol-Mediated Gamma Interferon Reduction Prevents Airway Inflammation and Airway Hyperresponsiveness in Respiratory Syncytial Virus-Infected Immunocompromised Mice

ABSTRACT Respiratory syncytial virus (RSV) is the most important cause of severe, lower respiratory tract infections in infants, and RSV infections have been associated with chronic wheezing and asthma during childhood. However, the mechanism of RSV-induced airway inflammation and airway hyperresponsiveness (AHR) is poorly understood. Furthermore, there are presently neither effective vaccines nor drugs available for the prevention or treatment of RSV infections. In this study, we investigated the effect of the plant extract resveratrol as a means of preventing airway inflammation and attenuating RSV-induced AHR. Our data showed that resveratrol reduced RSV lung titers and the number of infiltrating lymphocytes present in bronchoalveolar lavage fluid (BALF) and reduced inflammation. Furthermore, resveratrol attenuated airway responses to methacholine following RSV infection and significantly decreased gamma interferon (IFN-γ) levels in BALF of RSV-infected mice. Data presented in this report demonstrated that resveratrol controlled Toll-like receptor 3 (TLR3) expression, inhibited the TRIF signaling pathway, and induced M2 receptor expression following RSV infection. These data support a role for the use of resveratrol as a means of reducing IFN-γ levels associated with RSV-mediated airway inflammation and AHR, which may be mediated via TLR3 signaling.

Nebulized hypertonic saline treatment in hospitalized children with moderate to severe viral bronchiolitis.

The objective of this study was to determine the efficacy and safety of frequently inhaled nebulized hypertonic saline (HS) in infants with moderate to severe bronchiolitis. One hundred and twenty-six infants were randomized to receive either nebulized 3% hypertonic saline (HS) or 0.9% normal saline (NS), but only 112 patients completed the whole study. Cough, wheezing, pulmonary physical signs, clinical severity scores and the hospital length of stay (LOS) were recorded. The wheezing remission time was 4.8 ± 1.0 days in the NS group and 3.6 ± 0.9 days in the HS group (p <0.01). The cough remission time was 5.5 ± 0.9 days in the NS group and 4.3 ± 0.7 days in the HS group (p <0.01). The moist crackles disappeared at 6.2 ± 0.7 days in the NS group and at 4.4 ± 0.9 days in the HS group (p <0.01). The clinical severity scores decreased more significantly in the HS group than in the NS group on each day within 96 h after enrolment (p <0.01). The LOS decreased from 6.4 ± 1.4 days in the NS group to 4.8 ± 1.2 days in the HS group (p <0.01). The treatment was well tolerated, with no adverse effects attributable to nebulized HS. The conclusions are that frequently inhaled HS relieved symptoms and signs faster than NS, and shortened LOS significantly for infants with moderate to severe bronchiolitis, without apparent adverse effects.

Resveratrol Inhibits Respiratory Syncytial Virus-Induced IL-6 Production, Decreases Viral Replication, and Downregulates TRIF Expression in Airway Epithelial Cells

Respiratory syncytial virus (RSV) is the most common pathogen responsible for lower respiratory diseases in children. So far, there is no effective treatment or preventative vaccine available for RSV infection, although ribavirin and dexamethasone are commonly prescribed. Resveratrol has been shown to inhibit the replication of several other viruses, thus the effect of resveratrol on RSV-induced inflammatory mediators in 9HTEo cell cultures was evaluated, and possible mechanisms of action were explored and compared with dexamethasone and ribavirin. Incubation with resveratrol resulted in decreased IL-6 production and partial inhibition of RSV replication. Resveratrol treatment also inhibited virus-induced TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK binding kinase 1 (TBK1) protein expression. These data demonstrate the ability of resveratrol to inhibit cytokine production by RSV in airway epithelial cells, indicating that it might be a therapeutic agent with both anti-inflammatory and antiviral potential for the treatment of RSV infection.

Effects of prednisolone on refractory mycoplasma pneumoniae pneumonia in children.

To prospectively evaluate prednisolone treatment in children with refractory Mycoplasma pneumonia pneumonia (MPP).

Detection of enterovirus 68 as one of the commonest types of enterovirus found in patients with acute respiratory tract infection in China.

Human enterovirus 68 (HEV-68) is an enterovirus associated with respiratory illness. In China, no information about HEV-68 is available for children yet. This study aimed to investigate the presence of HEV-68 in mainland China between 2009 and 2012 and to explore the migration events of HEV-68 across the world. Among 1565 samples tested from children, 41 (2.6%) were positive for HEV and 223 (14.3%) for human rhinovirus (HRV). Seven (17.1%) of 41 HEVs were HEV-68. Two HEV-68- and five HRV-positive samples were detected in 585 adult samples. HEV-68 is the predominant type of enterovirus in children with acute respiratory tract infection (ARTI), followed by HEV-71 and coxsackievirus A6. Three HEV-68-infected children presented with severe pneumonia and one presented with a severe asthma attack. The viruses were attributed to two novel distinct sublineages of HEV-68 based on phylogenetic analysis of partial VP1 gene sequences. Migration events analysis showed that the USA and the Netherlands were possible geographical sources of HEV-68, from where three strains migrated to China. In conclusion, HEV-68 may play a predominant role among the enteroviruses associated with ARTI in children. Additional surveillance is needed to clarify the reason why HEV-68 causes such a wide spectrum of disease, from asymptomatic to severe respiratory disease and even death.

Lipopolysaccharide induces IL-6 production in respiratory syncytial virus-infected airway epithelial cells through the toll-like receptor 4 signaling pathway.

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis in young children. Microbial agents such as endotoxin and RSV are implicated in airway inflammation during the development of reactive airway disease (RAD) later in childhood. Toll-like receptors (TLRs) are involved in an inflammation cascade through pathogen-associated molecular pattern recognition including lipopolysaccharide (LPS) and viral components. In this study, we investigated the expression of TLRs and cytokine-chemokine production profiles of RSV-infected epithelial cells. In live-RSV infected human tracheal epithelial cell line (9HTEo), TLRs 1–10 mRNA levels were up-regulated in a time-dependent manner compared with ultraviolet (UV)-inactivated RSV. RSV was shown to alter TLR4 membrane and cytosolic location in epithelial cells. Stimulating RSV-infected epithelial cells with TLR4 agonist LPS increased synthesis of IL-6, IL-8, and reduced regulated on activation, normal T cell expressed and secreted (RANTES) production. TLR4 neutralizing antibody HTA125 and TLR4-targeting RNA interference experiments revealed that TLR4 signaling pathway played a predominant role in mediating LPS-induced-IL-6 production of RSV infected epithelial cells. Altogether, our studies indicated that TLR4 play a critical role in leading LPS mediated-IL-6 response in RSV infected-epithelial cells and might be an important factor influencing the cytokine-chemokine profile of epithelial cells interacting with virus and endotoxin, which is correlated with phenotypes of RSV diseases.

High Viral Load of Human Bocavirus Correlates with Duration of Wheezing in Children with Severe Lower Respiratory Tract Infection

Background Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI. Methods Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay. Results Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (>104 copies/mL) and the other sixteen samples had a low viral load (<104 copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV. Conclusion We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI, which led to more severe lower respiratory tract symptom, longer duration of wheezing and hospitalization.