Project description:BACKGROUND:Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. METHODS:Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. RESULTS:We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. CONCLUSION:Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.
Project description:Analysis of the DNA methylation level in peripheral blood leukocytes from healthy children using the Illumina HumanMethylation450 BeadChip Groupings by family membership requested but not provided by submitter
Project description:Analysis of the DNA methylation level in peripheral blood leukocytes from healthy children using the Illumina HumanMethylation450 BeadChip Groupings by family membership requested but not provided by submitter
Project description:Analysis of the DNA methylation level in peripheral blood leukocytes from healthy children using the Illumina HumanMethylation450 BeadChip Groupings by family membership requested but not provided by submitter DNA methylation association study in healthy children
Project description:Analysis of the DNA methylation level in peripheral blood leukocytes from healthy children using the Illumina HumanMethylation450 BeadChip Groupings by family membership requested but not provided by submitter DNA methylation association study in healthy children
Project description:Human coronaviruses (HCoVs) have been detected in children with upper and lower respiratory symptoms, but little is known about their relationship with severe respiratory illness.To compare the prevalence of HCoV species among children hospitalized for acute respiratory illness and/or fever (ARI/fever) with that among asymptomatic controls and to assess the severity of outcomes among hospitalized children with HCoV infection compared with other respiratory viruses.From December 2003 to April 2004 and October 2004 to April 2005, we conducted prospective, population-based surveillance of children <5 years of age hospitalized for ARI/fever in 3 US counties. Asymptomatic outpatient controls were enrolled concurrently. Nasal/throat swabs were tested for HCoV species HKU1, NL63, 229E, and OC43 by real-time reverse-transcription polymerase chain reaction. Specimens from hospitalized children were also tested for other common respiratory viruses. Demographic and medical data were collected by parent/guardian interview and medical chart review.Overall, HCoV was detected in 113 (7.6%) of 1481 hospitalized children (83 [5.7%] after excluding 30 cases coinfected with other viruses) and 53 (7.1%) of 742 controls. The prevalence of HCoV or individual species was not significantly higher among hospitalized children than controls. Hospitalized children testing positive for HCoV alone tended to be less ill than those infected with other viruses, whereas those coinfected with HCoV and other viruses were clinically similar to those infected with other viruses alone.In this study of children hospitalized for ARI/fever, HCoV infection was not associated with hospitalization or with increased severity of illness.
Project description:ObjectivesAcute Respiratory Infection (ARI) is the most common cause of childhood morbidity and mortality in developing countries, including Haiti. Our objective was to detect pathogens found in children with ARI in rural Haiti to help develop evidence-based guidelines for treatment and prevention.MethodsRetrospective study of students with ARI at four schools in rural Haiti. Viral and/or bacterial pathogens were identified by qPCR in 177 nasal swabs collected from April 2013 through November 2015.ResultsMost common viruses detected were Rhinovirus (36%), Influenza A (16%) and Adenovirus (7%), and bacteria were Streptococcus pneumoniae (58%) and Staphylococcus aureus (28%). Compared to older children, children aged 3-5 years had more Influenza A (28% vs. 9%, p=0.002) and Adenovirus detected (14% vs. 3%, p=0.01). Similarly, S. pneumoniae was greatest in children 3-5 years old (71% 3-5yrs; 58% 6-15 years; 25% 16-20 years; p=0.008). Children 3-10 years old presented with fever more than children 11-20 years old (22% vs 7%; p=0.02) and were more often diagnosed with pneumonia (28% vs 4%, p<0.001).ConclusionsYounger children had increased fever, pneumonia, and detection of Influenza A and S. pneumoniae. These data support the need for influenza and pneumococcus vaccination in early childhood in Haiti.
Project description:Children living in low socioeconomic communities are vulnerable to poor health outcomes, especially when critically ill. The purpose of this study was to investigate the association between socioeconomic status (SES) and illness severity upon pediatric intensive care unit (PICU) admission in children with acute respiratory failure. This secondary analysis of the multicenter Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial includes children, 2 weeks to 17 years old, mechanically ventilated for acute respiratory failure; specifically, subjects who had parental consent for follow-up and residential addresses that could be matched with census tracts (n = 2006). Subjects were categorized into quartiles based on income, with a median income of $54,036 for the census tracts represented in the sample. Subjects in the highest income quartile were more likely to be older, non-Hispanic White, and hospitalized for pneumonia. Subjects in the lowest income quartile were more likely to be Black, younger, and hospitalized for asthma or bronchiolitis, to have age-appropriate baseline functional status, and history of prematurity and asthma. After controlling for age group, gender, race, and primary diagnosis, there were no associations between income quartile and either Pediatric Risk of Mortality scores or pediatric acute respiratory distress syndrome. As measured, income-based SES was not associated with illness severity upon PICU admission in this cohort of patients. More robust and reliable methods for measuring SES may help to better explain the mechanisms by which socioeconomic affect critical illness.