Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)

Abstract

BackgroundRespiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics.Methods/designThe cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses.DiscussionIn the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment.With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.

Differences in the Nasopharyngeal Microbiome During Acute Respiratory Tract Infection With Human Rhinovirus and Respiratory Syncytial Virus in Infancy

“…The severity of the ARI was measured with the respiratory severity score (RSS) [9]. The diagnosis of HRV or RSV infection was made by quantitative reverse-transcription polymerase chain reaction [8]. We compared 52 infants with HRV ARI to 83 infants with RSV ARI.…”

“…The detailed methods for INSPIRE have been previously reported [8]. One parent of each infant provided informed consent for participation.…”

“…We have previously described the methods for nasopharyngeal sampling, viral detection, and characterization of the nasopharyngeal microbiome in detail [5,8,10]. In brief, after cell lysis and extraction of the microbial genomic DNA from the nasal wash samples, the V4 region of the 16S rRNA was amplified with 515F/806R primers.…”

“…To test this hypothesis, we assessed the nasopharyngeal microbiome among infants enrolled in the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (IN-SPIRE) study who met prespecified criteria for ARIs [8]. In these infants, we used next-generation sequencing of the 16S ribosomal RNA (rRNA) to compare the nasopharyngeal microbiome of infants with viral ARIs due to HRV and RSV.…”

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

“…This is a population-based birth cohort, and respiratory illness surveillance was performed every 2 weeks during the winter season. All information was prospectively collected, and parents gave their informed consent for study inclusion (42).…”