RT info:eu-repo/semantics/doctoralThesis
T1 Factores ambientales e inmunológicos asociados a la gravedad de la infección por virus respiratorio sincitial en pediatría
A1 Goez Sanz, María del Carmen
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Pediatría - Enfermedades por virus
K1 Environmental factors
K1 Factores ambientales
K1 Contamination
K1 Contaminación
K1 Respiratory syncytial virus
K1 Virus respiratorios sincitial
K1 Gene expression
K1 Expresión génica
K1 32 Ciencias Médicas
AB Introduction:Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (LRTI) in children under two years of age. Several factors, intrinsic and extrinsic to the patient, determine the severity of the disease.Objectives:1.- To evaluate the association of meteorological conditions and air pollution with hospital admissions for acute viral LRTI in children under two years of age.2.- To analyze whether the expression of inflammatory and antiviral genes in the peripheral blood of children under two years of age with RSV bronchiolitis is associated with severe hypoxemia and disease progression.Material and methods:Three studies were designed:1.- Environmental factors and pollutants: A bidirectional case-crossover study was conducted on 30,445 children with acute LRTI under two years of age, using data from the Minimum Basic Data Set (CMBD) between 2013 and 2015. Environmental data were obtained from the State Meteorological Agency (AEMET). The association was evaluated using conditional logistic regression.2.- Expression of inflammatory and antiviral genes and hypoxemia: A cross-sectional study was conducted on 121 RSV-infected children requiring hospital admission between 2015 and 2023. Total RNA was extracted from blood samples, and gene expression (IL-6, TNFα, CXCL8, ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10) was evaluated by quantitative polymerase chain reaction (qPCR). The outcome variable was severe hypoxemia (SpO2 ≤90%) at the time of hospital admission. Association analysis was performed using a volcano plot, logistic regression adjusted for relevant clinical variables, and orthogonal partial least squares discriminant analysis (OPLS-DA).3.- Expression of inflammatory and antiviral genes and progression of bronchiolitis: A prospective study was conducted on 117 infants between 2015 and 2023. The expression levels of nine inflammatory and antiviral genes were quantified by PCR. The infants were classified according to their evolution during admission into two groups: (i) no progression (n=74) and (ii) unfavorable progression (n=43). The association analysis was performed using logistic regression, adjusted for age, sex, prematurity, and severity.Results:Study 1: Lower temperatures one week before hospitalization (q=0.012) and higher relative humidity one and two weeks before the event (q=0.003 and q<0.001, respectively) were associated with a higher probability of hospital admission. In addition, higher levels of NO2 two weeks before the event were also associated with increased hospital admissions (q<0.001). Finally, on the event day, higher concentrations of SO2 (compared with 1-week (q=0.026) and 2-week (q<0.001) lags), O3 (compared with 3-day (q<0.001), 1-week (q<0.001), and 2-week (q<0.001) lags), and PM10 (compared with 2-week (q<0.001) lag) were associated with increased odds of viral LRTI hospital admissions.Study 2: We found that CXCL8 was overexpressed (>2-fold; q<0.05) in children with severe hypoxemia, whereas ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10 were underexpressed (<-2-fold; q<0.05). These associations were confirmed by adjusted logistic regression. OPLS-DA analysis showed that gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had variable importance in projection values (VIP) ≥1, being the most relevant features.Study 3: Univariate logistic models showed that low TNFα and CCL5 expression levels at baseline were associated with unfavorable RSV bronchiolitis progression. This was confirmed by multivariate analysis: TNFα (aOR=0.8; 95% CI=0.64 - 0.99; p=0.038) and CCL5 (aOR=0.76; 95% CI=0.62 - 0.93; p=0.007).Conclusions:1.- Short-term exposure to environmental factors, such as weather conditions and pollutants, is related to increased hospitalizations in children with acute LRTI under two years of age.2.- An imbalance in the innate response that favors inflammation over antiviral defense could contribute to severe hypoxemia in RSV-infected children.3.- An inadequate immune response against RSV, characterized by low levels of CCL5 and TNFα gene expression in peripheral blood, was associated with an unfavorable evolution of RSV bronchiolitis.
YR 2025
FD 2025
LK https://uvadoc.uva.es/handle/10324/75320
UL https://uvadoc.uva.es/handle/10324/75320
LA spa
NO Escuela de Doctorado
DS UVaDOC
RD 02-jun-2025