Qingkailing Injection () for Treatment of Children Pneumonia Induced by Respiratory Syncytial Virus: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of Qingkailing Injection (, QKL) for treatment of children pneumonia caused by respiratory syncytial virus (RSV). METHODS: Randomized clinical trials (RCTs) comparing QKL with ribavirin injection in the treatment of children pneumonia induced by RSV were searched in PubMed, Science Direct, Cochrane Library, Chinese VIP database, CNKI and Wanfang databases from their inception to March 2014. Meta-analyses were performed using RevMan 5.2 software. The methodological quality of the selected RCTs was evaluated by the Modified Jadad Score. The primary outcome measures were effective rate and the secondary outcomes were relief time of fever and cough. RESULTS: Seven RCTs with 992 cases published from 2008 to 2013 were identified. The meta-analysis results indicated that QKL was more effective in cure rate [risk ratios (RR)=1.32, 95% CI (1.17, 1.50), P<0.01], total effective rate [RR=1.07, 95% CI (1.02, 1.13), P=0.009] and less fever clearance time [mean difference=-0.73, 95% CI (-1.22,-0.23), P=0.004], compared with ribavirin injection in the treatment of RSV-induced children pneumonia. No dead case was reported in all trials. There were 3 trials mentioned adverse events, 2 reported no obvious adverse event occurred while 1 reported adverse events described as skin hypersensitivity, elevation of ALT, a mild abnormal of hepatic and renal function in both QKL and ribavirin group. CONCLUSIONS: QKL was an effective and relatively safe option for the treatment of RSV-induced children pneumonia. These therapeutic effects were promising but need to be interpreted with caution due to variations in the treatment and methodological weakness in the studies.

BuShenYiQi Formula strengthens Th1 response and suppresses Th2-Th17 responses in RSV-induced asthma exacerbated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of allergic asthma has been increased rapidly in recent years. About 20% of all these sufferers have experienced asthma exacerbation. Although corticosteroids and ß-agonists therapy improves serious asthma symptoms, they can׳t completely cure these allergic diseases. BuShenYiQi Formula (BSYQF) has been widely used to treat bronchial asthma and its exacerbation for decades in Huashan Hospital of Fudan University, China. Nevertheless, the mechanisms of BSYQF' anti-asthmatic effects haven׳t been fully elucidated. In this study, we evaluated the involvement of Th1, Th2 and Th17 cells in the anti-asthmatic effects of BSYQF in Respiratory Syncytial Virus (RSV)-induced asthma exacerbated mice. MATERIALS AND METHODS: BALB/c mice were challenged with ovalbumin (OVA), followed by RSV infections for establishment of asthma exacerbated model. Airway hyperresponsiveness (AHR) was examined by direct airway resistance analysis. Bronchoalveolar lavage fluid (BALF) was assessed for inflammatory cell counts and secreted levels of cytokines. Lung tissues were detected for inflammatory cell infiltration and mucus hypersecretion. Subsequently, CD4(+)T cells and alveolar macrophages were sorted and purified from mice lungs in different groups. CD4(+)T cell subpopulations including the expression levels of important transcription factors in T lymphocyte polarization were examined. In asthma exacerbation group, the purified CD4(+)T cells and macrophages were co-cultured, and the changes of co-cultured cells with BSYQF treatment were further analyzed in vitro. RESULTS: BSYQF significantly attenuated airway hyperresponsiveness and inhibited inflammatory cell infiltration, especially for excessive infiltration of eosinophils and neutrophils. Histopathological analysis showed that BSYQF could suppress airway inflammation and RSV replication. The decreases of antigen-specific IgE, IL-4, IL-5, IL-6, IL-17a and increases of IFN-γ, IL-12 were observed in BALF, lung homogenate or serum after BSYQF treatment. We further confirmed that BSYQF could down-regulate Th2-Th17 cell proportions with lower expressions of GATA3, STAT6 and RORγT, and up-regulate Th1 cell proportion with higher expression of T-bet. And as a result of strengthened Th1-response, activated macrophages were also observed by remarkable enhancement of signature gene expressions and phagocytosis. CONCLUSIONS: BSYQF can significantly attenuate RSV-induced asthma exacerbation. These effects may be mediated at least partially by regulating the balance between Th1 and Th2-Th17 responses.

Arginine appearance and nitric oxide synthesis in critically ill infants can be increased with a protein-energy-enriched enteral formula.

BACKGROUND: Arginine is considered an essential amino acid during critical illness in children, and supplementation of arginine has been proposed to improve arginine availability to facilitate nitric oxide (NO) synthesis. Protein-energy-enriched enteral formulas (PE-formulas) can improve nutrient intake and promote anabolism in critically ill infants. However, the effect of increased protein and energy intake on arginine metabolism is not known. OBJECTIVE: We investigated the effect of a PE-formula compared with that of a standard infant formula (S-formula) on arginine kinetics in critically ill infants. DESIGN: A 2-h stable-isotope tracer protocol was conducted in 2 groups of critically ill infants with respiratory failure because of viral bronchiolitis, who received either a PE-formula (n = 8) or S-formula (n = 10) in a randomized, blinded, controlled setting. Data were reported as means ± SDs. RESULTS: The intake of a PE-formula in critically ill infants (aged 0.23 ± 0.14 y) resulted in an increased arginine appearance (PE-formula: 248 ± 114 µmol · kg(-1) · h(-1); S-formula: 130 ± 53 µmol · kg(-1) · h(-1); P = 0.012) and NO synthesis (PE-formula: 1.92 ± 0.99 µmol · kg(-1) · h(-1); S-formula: 0.84 ± 0.36 µmol · kg(-1) · h(-1); P = 0.003), whereas citrulline production and plasma arginine concentrations were unaffected. CONCLUSION: In critically ill infants with respiratory failure because of viral bronchiolitis, the intake of a PE-formula increases arginine availability by increasing arginine appearance, which leads to increased NO synthesis, independent of plasma arginine concentrations. This trial was registered at www.trialregister.nl as NTR515.

Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing. METHODS: A retrospective cohort study examined children born at ≥32 weeks gestation between 1996-2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32-33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03-1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49-4.50). CONCLUSIONS: Laboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.

Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI. OBJECTIVE: To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI. DESIGN: A prospective birth cohort study was performed in healthy term neonates. Concentrations of 25-hydroxyvitamin D (25-OHD) in cord blood plasma were related to RSV LRTI in the first year of life, defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen. RESULTS: The study population included 156 neonates. Eighteen (12%) developed RSV LRTI. The mean plasma 25-OHD concentration was 82 nmol/L. Overall, 27% of neonates had 25-OHD concentrations < 50 nmol/L, 27% had 50-74 nmol/L and only 46% had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy. Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not (65 nmol/L versus 84 nmol/L, P = .009). Neonates born with 25-OHD concentrations <50 nmol/L had a sixfold (95% confidence interval: 1.6-24.9; P = .01) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥ 75 nmol/L. CONCLUSIONS: Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life. Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy.

Recurrent wheezing in the third year of life among children born at 32 weeks' gestation or later: relationship to laboratory-confirmed, medically attended infection with respiratory syncytial virus during the first year of life.

OBJECTIVE: To quantify the relationship between recurrent wheezing (RW) in the third year of life and respiratory syncytial virus (RSV) infection, prematurity, and neonatal oxygen exposure. DESIGN: Retrospective cohort study linking inpatient, outpatient, and laboratory databases for cohort assembly and logistic regression analysis. SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: A total of 71,102 children born from 1996 to 2002 at 32 weeks' gestational age or later who were health plan members for 9 or more months in their first and third years. MAIN EXPOSURES: Laboratory-confirmed, medically attended RSV infection during first year and supplemental oxygen during birth hospitalization. OUTCOME MEASURES: Recurrent wheezing, quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The rate of RW in the third year of life was 16.23% among premature infants with RSV and 6.22% among those without RSV. The risk of RW increased among infants who had an RSV outpatient encounter (adjusted odds ratio [AOR], 2.07; 95% CI, 1.61-2.67), uncomplicated RSV hospitalization (AOR, 4.66; 95% CI, 3.55-6.12), or prolonged RSV hospitalization (AOR, 3.42; 95% CI, 2.01-5.82) compared with infants without RSV encounters. Gestational age of 34 to 36 weeks was associated with increased risk of RW (AOR, 1.23; 95% CI 1.07-1.41) compared with 38 to 40 weeks, while a gestational age of 41 weeks or more was protective (AOR, 0.90; 95% CI, 0.81-0.99). Supplemental oxygen exposure was associated with increased risk at all levels. CONCLUSION: Laboratory-confirmed, medically attended RSV infection, prematurity, and exposure to supplemental oxygen during the neonatal period have independent associations with the development of RW in the third year of life.

Critically ill infants benefit from early administration of protein and energy-enriched formula: a randomized controlled trial.

BACKGROUND & AIMS: Nutritional support improves outcome in critically ill infants but is impeded by fluid restriction, gastric intolerance and feeding interruptions. Protein and energy-enriched infant formulas may help to achieve nutritional targets earlier during admission and promote anabolism. METHODS: Randomized controlled design. Infants with respiratory failure due to RSV-bronchiolitis received a protein and energy-enriched formula (PE-formula, n=8) or a standard formula (S-formula, n=10) during 5 days after admission. PRIMARY OUTCOME: nutrient delivery, energy and nitrogen balance and plasma amino acid concentrations. Secondary outcome: tolerance and safety. RESULTS: Nutrient intakes were higher in PE fed infants and met population reference intake (PRI) on day 3-5 whilst in S-fed infants PRI was met on day 5 only. Cumulative nitrogen balance (cNB) and energy balance (cEB) were higher in PE-infants compared to S-infants (cNB: 866+/-113 vs. 296+/-71 mg/kg; cEB: 151+/-31 and 26+/-17 kcal/kg, both P<0.01). Essential amino acid levels were higher in PE-infants but within reference limits whereas below these limits in S-infants. Both formulas were well tolerated. CONCLUSIONS: Early administration of a protein and energy-enriched formula in critically ill infants is well tolerated, promotes a more adequate nutrient intake and improves energy and nitrogen balance without adverse effects.

4-Methoxycinnamaldehyde inhibited human respiratory syncytial virus in a human larynx carcinoma cell line.

4-Methoxycinnamaldehyde, an active constituent of Agastache rugosa, was examined for its cytoprotective activity against RSV by XTT method in human larynx carcinoma cell line. 4-Methoxycinnamaldehyde could effectively inhibit cytopathic effect of RSV (p<0.0001) with an estimated IC(50) of 0.055microg/ml and a selectivity index (SI) of 898.2. 4-Methoxycinnamaldehyde (0.03microg/ml) could inhibit viral entrance by interfering viral attachment (IC(50) of 0.06microg/ml; p<0.0001) and internalization (IC(50) of 0.01microg/ml; p<0.0001). 4-Methoxycinnamaldehyde significantly increased the basal production of IFN (p=0.0015), but not the virus-induced IFN production. Therefore, its cytoprotective activity against RSV was not mediated by interferon. In conclusion, 4-methoxycinnamaldehyde might be helpful to manage the disease induced by RSV infection.

An epidemiological study of respiratory syncytial virus associated hospitalizations in Denmark.

Respiratory syncytial virus (RSV) is the most common viral pathogen that causes lower respiratory tract infections in infants. Studies have implicated severe RSV infections early in life as a risk factor for subsequent development of reactive airway disease. We are conducting a study to validate RSV-associated diagnoses in the Danish National Patient Registry, to assess whether the incidence of severe RSV infection is increasing in Denmark, to identify predisposing and protective factors for RSV-associated hospitalization in Denmark, and to examine the association of severe RSV infection with reactive airway disease. The influence of various biological, social and environmental factors on hospitalization for RSV infection will be studied through several population-based registers, including the Danish National Birth Cohort: 'Better health for mothers and children'. The RSV hospitalization cases will be compared with control individuals selected within the same population groups on a case-control or a cohort basis in order to produce estimates of age-adjusted and sex-adjusted relative risks (odds ratio and relative risk) for hospitalization associated with various risk factors. Using register linkage and unique registration of exposures collected through interviews and blood samples from the Danish National Birth Cohort, we will be able to resolve the issues referred to above in a very large sample of Danish children.

Características del uso intrahospitalario de antibióticos en las infecciones respiratorias agudas bajas: campaña de invierno 1996 / Characteristics of the intrahospitalary use of antibiotics in acute lower respiratory infections: winter campaign, 1996

La mayoría de las infecciones respiratorias agudas bajas de los niños son de naturaleza viral y se deben mayoritariamente al virus respiratorio sincicial. Pueden, sin embargo, complicarse con infecciones bacterianas lo que implica el empleo de antibióticos. Esto encarece el tratamiento y complica el manejo de los pacientes. El trabajo se basa en la revisión de un material de 133 niños con infecciones respiratorias agudas bajas que recibieron antibióticos. Se describen las características clínicas de los pacientes, sus factores de gravedad y los resultados de algunos exámenes realizados (hemograma, sedimentación, proteína C reactiva, inmunofluorescencia indirecta), Se analizan las razones que justifican la administración de antibióticos, destacando que en 8,4 por ciento de los enfermos no parece haber existido una causa clara que lo explique. La penicilina y la quemicetina fueron los principales antibióticos utilizados

[Penicillin-resistant pneumococcal pneumonia (serotype p14), and coinfection with respiratory syncytial virus and Mycoplasma]. / Pleuro-pneumopathie à pneumocoque résistant à la pénicilline (sérotype p14), et co-infection à virus respiratoire syncytial et mycoplasme.

A 3-year old child was admitted for a pneumococcal pneumonia with pleural effusion, initially treated with amoxicillin and clavulanic acid. Clinical deterioration suggested a resistance to conventional antibiotics which was confirmed by bacteriological investigation. A co-infection with respiratory syncitial virus and Mycoplasma pneumoniae was associated. Under adapted antibiotherapy, the clinical course improved.

Respiratory syncytial virus infection: its role in aeroallergen sensitization during the first two years of life.

Our aim was to study the influence of infection with the respiratory syncytial virus (RSV) in non-hospitalized infants on sensitization to aeroallergens and the early manifestation of atopy. Six hundred and nine infants from the prospective German Multicenter Cohort Study on Atopy were included, 38% of whom had an elevated atopic risk. RSV IgG and IgM antibodies were tested by ELISA with gradient purified RSV antigen. Specific IgE against mites, cat dandruff, birch and grass pollens and relevant nutritional antigens were tested with CAP-RAST-FEIA (Pharmacia, Sweden). Of the cord sera 99% were positive for RSV-IgG, 44.7% at one year and 64.2% (n = 265) at two years of age. The positivity rate after 12 months varied with the season of birth, the number of siblings and the degree of exposure to tobacco smoke; and correlated closely with attacks of wheezing during infancy. Twenty (2.8%) children were found to be sensitized against at least one aeroallergen at one year, and 28 (10.5%) at two years. By the first birthday, mite sensitization (n = 3) could only be seen in the RSV-infected children; grass pollen sensitization (n = 9) was associated with RSV seropositivity (logistic regression model including the confounders mentioned above: with RSV IgG < p = 0.048 > and IgM < p = 0.0006 >), as was birch sensitization (n = 5) with RSV IgM (p = 0.009). No such differences could be detected at two years. No correlation of RSV seropositivity to any allergic manifestation could be found. We conclude, that it is only in the first year of life, that RSV infection plays a significant role in promoting sensitization against aeroallergens, which do not at this time produce allergic symptoms.