Low peripheral blood chemokine (C-C motif) ligand 5 and tumor necrosis factor α gene expression is associated with unfavorable progression of respiratory syncytial virus bronchiolitis in infants.

OBJECTIVES: We aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants' peripheral blood is associated with bronchiolitis progression. METHODS: We conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room. RESULTS: Infants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007). CONCLUSIONS: An inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis.

Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study.

OBJECTIVE: This study evaluated the association of the short-term exposure to environmental factors (relative humidity, temperature, NO2, SO2, O3, PM10, and CO) with hospital admissions due to acute viral lower respiratory infections (ALRI) in children under two years before the COVID-19 era. METHODS: We performed a bidirectional case-crossover study in 30,445 children with ALRI under two years of age in the Spanish Minimum Basic Data Set (MBDS) from 2013 to 2015. Environmental data were obtained from Spain's State Meteorological Agency (AEMET). The association was assessed by conditional logistic regression. RESULTS: Lower temperature one week before the day of the event (hospital admission) (q-value = 0.012) and higher relative humidity one week (q-value = 0.003) and two weeks (q-value<0.001) before the day of the event were related to a higher odds of hospital admissions. Higher NO2 levels two weeks before the event were associated with hospital admissions (q-value<0.001). Moreover, higher concentrations on the day of the event for SO2 (compared to lag time of 1-week (q-value = 0.026) and 2-weeks (q-value<0.001)), O3 (compared to lag time of 3-days (q-value<0.001), 1-week (q-value<0.001), and 2-weeks (q-value<0.001)), and PM10 (compared to lag time of 2-weeks (q-value<0.001)) were related to an increased odds of hospital admissions for viral ALRI. CONCLUSION: Short-term exposure to environmental factors (climatic conditions and ambient air contaminants) was linked to a higher likelihood of hospital admissions due to ALRI. Our findings emphasize the importance of monitoring environmental factors to assess the odds of ALRI hospital admissions and plan public health resources.

Patrones de excreción del virus de la gripe A (H1N1)pdm09 en pacientes hospitalizados pediátricos / Influenza A (H1N1)pdm09 viral clearance kinetics in hospitalized children

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Complicaciones obstétricas y perinatales en la diabetes tipo 1: estudio retrospectivo unicéntrico / Obstetric and perinatal complications in type 1 diabetes: a retrospective single-center study

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Host and environmental factors influencing respiratory secretion of pro-wheezing biomarkers in preterm children.

Cytokines are actively secreted by the respiratory mucosa of preterm children and participate in the pathogenesis of wheezing. This study aimed to identify the factors that could potentially influence respiratory secretion of cytokines in these children. A nasopharyngeal aspirate (NPA) was collected from 77 preterm children 1 yr after birth. NPAs from 14 healthy, 1-yr-old term children were collected in parallel. 27 cytokines were measured in the NPAs using a multiplex assay. Multivariate stepwise regression analysis with Bonferroni correction evidenced that the variable [daycare attendance] was associated with higher levels of [monocyte chemoattractant protein-1 (MCP-1), IL-6, vascular endothelial growth factor (VEGF), IL-1ß, IL-10, tumor necrosis factor (TNF)-α]; [male sex] with higher levels of (MCP-1, VEGF, and IL-1ß); [smokers at home] was associated with higher levels of MCP-1 (p < 0.0013). In turn, [prophylaxis with palivizumab] was associated with lower levels of (IL-6, IL-7) (p < 0.0013). All these mediators participate in the pathogenesis of asthma and recurrent wheezing. Preterm children secreted higher levels of chemokines (interferon-gamma inducible protein-10, macrophage inflammatory protein-1α, Eotaxin, MCP-1), growth factors (platelet-derived growth factor-bb, VEGF, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor), Th1 (IL12, interferon-γ), Th2 (IL-9, IL-13), Th17 (IL-6, IL-17) cytokines, and immunomodulatory mediators (IL1RA and granulocyte colony-stimulating factor) than term children. In conclusion, we have identified for the first time a group of individual and environmental factors influencing respiratory secretion of cytokines in preterm children at the long term after birth. To know these factors could help to prevent the instauration of conditions linked to the appearance of chronic respiratory diseases such as wheezing or asthma.

Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is an important cause of recurrent wheezing in infants. Nevertheless, the link between RSV infection and wheezing has yet to be elucidated at the molecular level. Here, we present a preliminary study on the evolution of the immune response in the respiratory tract at long-term after RSV infection. Twenty-seven immune mediators were profiled in nasopharyngeal aspirates (NPAs) obtained from 20 children hospitalized due to a severe infection by RSV at discharge from hospital and again 1 yr later. The same mediators were profiled in parallel in NPAs from 12 healthy controls. In the year following discharge, 85% (17/20) of children of the RSV group suffered at least one episode of wheezing documented by the pediatrician. On the contrary, wheezing episodes were observed only in 25% (3/12) of children in the control group. While most of the mediators profiled returned to normal levels by 1 yr after discharge from hospital, RSV children showed a persistent nasal hyper-secretion of VEGF, G-CSF, IL-10, IL-6, IFN-gamma, IL-7 and IL-13. In previous works VEGF, IL-10 and IFN-gamma have been put in relation with the pathogenesis of post-virus induced asthma. G-CSF, IL-6, IL-7 and IL-13 are increased in respiratory and plasma samples of asthmatic patients. Here, we evidence for the first time a persistent elevation of these mediators as late as 1 yr after severe RSV disease resolution, reinforcing their possible implication in the pathogenesis of wheezing.

Similar cytokine profiles in response to infection with respiratory syncytial virus type a and type B in the upper respiratory tract in infants.

Human respiratory syncytial virus (RSV) is the leading viral cause of severe respiratory illness in infants and young children worldwide. RSV isolates can be divided into 2 subgroups, type A and type B. Here, we compare for the first time the nasal profiles of 27 immune mediators in response to both viral subtypes in 14 children infected with RSV/A, 8 children infected with RSV/B, 11 children coinfected with RSV/A plus other respiratory viruses, and finally, 27 control children, all <2 years old. Our results evidence that children's infection with both RSV subtypes induces very similar profiles of immune mediators in the upper respiratory tract, characterized by the elevation of Th1 and Th2 cytokines, chemokines and growth factors. Interestingly, no major differences in the profiles of the immune mediators were found between the children infected exclusively with RSV/A and those infected with RSV/A plus other respiratory viruses.

Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children.

UNLABELLED: Profiling of immune mediators in both nasal and plasma samples is a common approach to the study of pathogenesis in respiratory viral infections. Nevertheless, mucosal immunity functions essentially independently from peripheral immunity. In our study, 27 immune mediators were profiled in parallel, in nasopharyngeal aspirates (NPAs) and plasma from 22 < 2 year-old children with a severe respiratory syncytial virus infection involving the lower respiratory tract, using a multiplex assay. NPAs from 22 children with innocent heart murmurs were used as controls. Differences in mediator concentrations between NPAs from patients and controls were assessed using the Mann-Whitney test. Ratios of innate/adaptive-immunity mediators, Th2/Th1-cytokines and CXC/CC-chemokines were calculated for NPAs and plasmas and differences were assessed using the Wilcoxon test. Associations mediators, severity and leukocyte counts were studied using the Spearman-Karber test. RESULTS: increased levels of Th1 cytokines (IL-1beta, IL-2, IL-12p70, IFNgamma, TNFalpha), Th2 cytokines (IL-13, IL-4, IL-6, IL-10), chemokines (IP-10, IL-8, MIP1alpha, MIP-1beta), growth factors (FGFb, PDGFbb, GCSF) and IL-1RA, IL-17 were observed in patient NPAs in comparison to controls. In the relative comparisons between patient NPAs and plasmas, a predominance of innate immunity mediators, Th2 cytokines and CXC chemokines was found at the mucosal level. No association between the level of each mediator in NPAs and plasma was found. In plasma, PDGFbb, VEGF, MIP-1alpha, IL-8 correlated with severity; RANTES and IL-6 correlated with leukocyte counts. CONCLUSIONS: acute respiratory syncytial virus infection induces a relative predominance of innate-immunity mediators, Th2 cytokines and CXC chemokines in the mucosal compartment in infected children.