Longitudinal Associations Between Respiratory Infections and Asthma in Young Children.
Ontology highlight
ABSTRACT:
SUBMITTER: Ramette A
PROVIDER: S-EPMC6070097 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundGenome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in early childhood is unclear.MethodsWe analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 preselected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies.ResultsThe asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01-1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01-1.20, P = .03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses.ConclusionsAsthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors. Clinical Trials Registration. NCT00494624 and NCT00731575.
| S-EPMC10582910 | biostudies-literature
Project description:ObjectiveTo complete a systematic review of the literature describing associations between all environmental exposures and asthma symptoms and exacerbations in children up to mean age of 9 years.DesignSystematic review.SettingReference lists of identified studies and reviews were searched for all articles published until November 2013 in electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Controls Trials Register).ParticipantsStudies were selected which examined a link between exposure to environmental factors and asthma symptoms and exacerbations where the study participants were children with a mean age of ≤9 years.Primary and secondary outcome measuresIndices of asthma symptoms, control and exacerbations.ResultsA total of 27 studies were identified including eight where inhaled allergens and four where environmental tobacco smoke (ETS) were the exposures of interest. There was evidence that exposure to allergen, ETS, poor air quality and unflued heaters had a modest magnitude of effect (ORs between 2 and 3). There was also evidence of interactions observed between exposures such as allergen and ETS.ConclusionsExposure to inhaled allergens, ETS, unflued heaters and poor air quality has an important effect on exacerbations in young children with asthma and should be minimised or, ideally, avoided. Better understanding of the effect of exposure to damp housing, air conditioning and dietary factors plus interactions between environmental exposures associated with exacerbations is required.
| S-EPMC3927936 | biostudies-literature
Project description:High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease.We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18-2.16), M. catarrhalis (1.78, 1.29-2.47), human rhinoviruses (1.63, 1.19-2.22) and enteroviruses (1.97, 1.26-3.10), and negatively associated with S. aureus presence (0.59, 0.35-0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22-2.18) and respiratory syncytial viruses (2.78, 1.06-7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01-3.93) and adenoviruses (3.69, 1.29-10.56), and negatively with S. aureus carriage (0.42, 0.25-0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59-14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66-3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses.Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.
| S-EPMC3474735 | biostudies-literature
Project description:Background: Genetic heterogeneity in the innate immune system may account for variable susceptibility to respiratory tract infections (RTIs) in children. Objective: We aimed to assess the impact of polymorphisms rs273259 and rs1333969 in type I interferon related gene IFI44L on susceptibility to RTIs and acute otitis media in children. Methods: In two prospective, population-based birth cohorts, the FinnBrain Birth Cohort Study and the STEPS Study, IFI44L genotypes for rs273259 and rs1333969 were determined in relation to the development of RTIs until one and two years of age, respectively, and adjusted incidence rate ratios (aIRR) or odds ratios (OR) were calculated. At age 3 months, whole blood transcriptional profiles were analyzed and nasal samples were tested for respiratory viruses in a subset of children. Results: In respiratory virus-positive children at 3 months of age, IFI44L gene variants were associated with decreased expression levels of IFI44L and several other interferon related genes. Conclusions: Variant forms of IFI44L gene were protective against early-childhood RTIs or acute otitis media in two independent birth cohorts, and they attenuated interferon pathway activation by respiratory viruses.
2020-08-18 | GSE150133 | GEO
Project description:BACKGROUND:Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. OBJECTIVE:We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. METHODS:We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. RESULTS:Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ?5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. CONCLUSION:Urban children with asthma with high-symptom respiratory viral infections have reduced FEF25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.
| S-EPMC6360098 | biostudies-literature
Project description:Human Respiratory Syncytial Virus and Human Rhinovirus are the most frequent cause of respiratory tract infections in infants and children and are major triggers of acute viral bronchiolitis, wheezing and asthma exacerbations. Here, we will discuss the application of the powerful tools of systems biology to decode the molecular mechanisms that determine risk for infection and subsequent asthma. An important conceptual advance is the understanding that the innate immune system is governed by a Bow-tie architecture, where diverse input signals converge onto a few core pathways (e.g., IRF7), which in turn generate diverse outputs that orchestrate effector and regulatory functions. Molecular profiling studies in children with severe exacerbations of asthma/wheeze have identified two major immunological phenotypes. The IRF7hi phenotype is characterised by robust upregulation of antiviral response networks, and the IRF7lo phenotype is characterised by upregulation of markers of TGF? signalling and type 2 inflammation. Similar phenotypes have been identified in infants and children with severe viral bronchiolitis. Notably, genome-wide association studies supported by experimental validation have identified key pathways that increase susceptibility to HRV infection (ORMDL3 and CHDR3) and modulate TGF? signalling (GSDMB, TGFBR1, and SMAD3). Moreover, functional deficiencies in the activation of type I and III interferon responses are already evident at birth in children at risk of developing febrile lower respiratory tract infections and persistent asthma/wheeze, suggesting that the trajectory to asthma begins at birth or in utero. Finally, exposure to microbes and their products reprograms innate immunity and provides protection from the development of allergies and asthma in children, and therefore microbial products are logical candidates for the primary prevention of asthma.
| S-EPMC7503410 | biostudies-literature
Project description:Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma.We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season.The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (COAST) birth cohort study.A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study.We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma.
| S-EPMC4715666 | biostudies-literature
Project description:BackgroundEpidemiology studies have shown that ambient concentrations of ozone and fine particulate matter (PM2.5) are associated with increased emergency department (ED) visits and hospital admissions (HAs) for asthma.ObjectiveEvaluate the impact of outdoor pollen, respiratory infections, and socioeconomic status (SES) on the associations between ambient ozone and PM2.5 and asthma HAs in New York City.MethodsDaily ozone, PM2.5, meteorological factors, pollen, and hospitalization records during 1999 to 2009 were obtained for New York City residents. Daily counts of HAs for asthma and respiratory infections were calculated for all-age and specific age groups, and for high- and low-SES communities. Generalized additive models were used to examine ambient concentrations of ozone and PM2.5 and asthma HAs, potential confounding effects of outdoor pollen and HAs for respiratory infections, and potential effect modification by neighborhood SES.ResultsBoth ozone and PM2.5 were statistically significantly associated with increased asthma HAs in children aged 6-18 years (per 10 ppb increase in ozone: RR = 1.0203, 95% CI: 1.0028-1.0382; per 10 ?g/m3 increase in PM2.5: RR = 1.0218, 95% CI: 1.0007-1.0434), but not with total asthma HAs, or asthma HAs in other age groups. These associations were stronger for children living in the high-SES areas. Adjustment for respiratory infection HAs at various lags did not result in changes greater than 10% in the risk estimates for either ozone or PM2.5. In contrast, adjustment for outdoor pollen generally attenuated the estimated RRs for both ozone and PM2.5.ConclusionsAmbient ozone and PM2.5 are associated with asthma HAs in school-age children, and these associations are not modified by SES. HAs for respiratory infections do not appear to be a confounder for observed ozone- and PM2.5-asthma HAs associations, but pollen may be a weak confounder.
| S-EPMC5515410 | biostudies-literature
Project description:Anelloviruses (AVs) are ubiquitous in humans and are the most abundant components of the commensal virome. Previous studies on the diversity, transmission, and persistence of AVs mainly focused on the blood or transplanted tissues from adults; however, the profile of the anellome in the respiratory tract in children are barely known. We investigated the anellome profile and their dynamics in the upper respiratory tract from a cohort of children with acute respiratory tract infections (ARTIs). Different to that in adult, betatorquevirus is the most abundant genus, followed by alphatorquevirus. We found that the relative abundance of betatorquevirus was higher in earlier time points, and in contrast, the abundance of alphatorquevirus was higher in later time points; these results might suggest that betatorquevirus decreased with age and alphatorquevirus increased with age in childhood. No difference regarding the diversity and abundance of anellome was found between single and multiple ARTIs, consistent with the idea that AV is not associated with certain disease. Most AVs are transient, and a small proportion (8 per cent) of them were found to be possibly persistent, with persistence time ranging from 1 month to as long as 56 months. Furthermore, the individual respiratory anellome appeared to be unique and dynamic, and the replacement of existing AVs with new ones are common over different time points. These findings demonstrate that betatorquevirus may be the early colonizer in children, and the individual respiratory anellome is unique, which are featured by both chronic infections and AV community replacement.
| S-EPMC10478798 | biostudies-literature
Project description:BackgroundHuman rhinovirus (RV) is the most common respiratory virus and has been associated with frequent and severe acute lower respiratory infections (ALRI). The prevalence of RV species among HIV-infected children in South Africa is unknown.ObjectivesTo describe the prevalence of respiratory viruses, including RV species, associated with HIV status and other clinical symptoms in children less than two years of age with and without ALRI in Pretoria, South Africa.Study designNasopharyngeal aspirates were collected from 105 hospitalized ALRI cases and 53 non-ALRI controls less than two years of age. HIV status was determined. Common respiratory viruses were identified by PCR, and RV species and genotypes were identified by semi-nested PCR, sequencing and phylogenetic tree analyses.ResultsRespiratory viruses were more common among ALRI cases than controls (83.8% vs. 69.2%; p=0.041). RV was the most commonly identified virus in cases with pneumonia (45.6%) or bronchiolitis (52.1%), regardless of HIV status, as well as in controls (39.6%). RV-A was identified in 26.7% of cases and 15.1% of controls while RV-C was identified in 21.0% of cases and 18.9% of controls. HIV-infected children were more likely to be diagnosed with pneumonia than bronchiolitis (p<0.01). RSV was not identified in any HIV-infected cases (n=15) compared with 30.6% of HIV-uninfected cases (n=85, p=0.013), and was identified more frequently in bronchiolitis than in pneumonia cases (43.8% vs. 12.3%; p<0.01).ConclusionsRV-A and RV-C are endemic in South African children and HIV infection may be protective against RSV and bronchiolitis.
| S-EPMC7106452 | biostudies-literature