title: The association between viral and bacterial acquisition in infancy and childhood lung health: a community-based birth cohort study
Creators: name: Takashima, Mari
Publisher: name: Griffith University
Year: 2024
Subjects: subject: respiratory viruses
subject: paediatric
subject: pathogens
subject: asthma

description: Infancy and early childhood are critical periods for immune system development and potential adverse effects from exposure to infectious diseases. Acute respiratory infections (ARIs) are common in the first 2 years of life. The most common virus associated with ARI in Australian preschool children is human rhinovirus (HRV), but respiratory syncytial virus (RSV) is responsible for the greatest number of hospitalisations. Most studies examining the impact of HRV and RSV have considered hospital-based cohorts, with relatively limited research exploring community-level disease burden. Emerging evidence indicates that detections of pathogens in early life are associated with poorer childhood respiratory health. This Thesis explores the epidemiology and community disease burden of RSV in young Australian children. It also investigates associations of early pathogen detection, particularly HRV and potentially pathogenic bacteria (PPB), antenatal exposures to maternal RSV antibodies and air pollution/greenspace, with respiratory outcomes such as wheezing episodes and asthma. Additionally, it examines the evidence for virus-virus interactions in early childhood. Data from the Observational Research in Childhood Infectious Diseases (ORChID) birth cohort study was used in this Thesis. Parents of children residing in Greater Brisbane between September 2010 and October 2014 provided pregnancy and birth details, weekly nasal swabs, daily symptoms, and healthcare use data. Overall, 158 children returned 11,126 swabs and 154 children provided 87,547 symptom diary-days. Eighty-five ORChID children subsequently participated in the ORChID extension study, Early Life Lung Function study, which tracked lung health annually from age 3 until 7 years. First, I described the epidemiology of RSV in the ORChID cohort. Incidence in the first 2 years of life was 0.46 (95% confidence interval (CI): 0.37, 0.58) episodes per child-year. Respiratory syncytial virus specific antibody seroprevalence was 94.4% at age 3 years. While 73.2% of infections were symptomatic, of whom 46.7% sought medical help, all except two (3.3%) were managed solely within the community. Viral load was higher in symptomatic than asymptomatic infections. Second, I used data from ORChID and the Perth-based Childhood Asthma Study to find that, in contrast to results from studies focusing upon hospitalisation, high levels of transplacental respiratory virus neutralising antibody (RSV-NA) may not decrease overall RSV infections in the first 6 months of life and may not protect against wheeze and asthma developing in early childhood at a community level. Cord-blood RSV-NA was also not associated with RSV-NA levels at age 3 years. Third, I examined the temporal sequence and thus the directionality of any interaction between HRV and other RNA respiratory viruses detected in the ORChID cohort. Human rhinovirus was the most commonly detected virus (n=2,058; 25.4% of higher-quality swabs), followed by human coronavirus (n=153; 1.9%) and RSV (n=90; 1.1%). New HRV detections were negatively associated with new RNA respiratory virus detections 1 week later (odds ratio (OR) 0.48; 95%CI: 0.13, 0.83), as were RNA virus detections with new HRV detections the following week (OR 0.34; 95%CI: 0.09, 0.60). A strong, negative bidirectional association between HRV and other RNA viruses with a refractory period of at least 1 week was demonstrated. Fourth, I evaluated the association between HRVs and PPB (Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae) during the first 3 months of life and wheeze in the first 2 years of life; and asthma at age 5-7 years. Each additional week of HRV detection increased the incidence of wheezing 1.16 times (95%CI: 0.99, 1.35) by age 2 years. Each additional week with H. influenzae increased the odds of asthma by 135% (odds ratio: 2.35, 95%CI:0.99, 5.58). No significant interaction was observed between HRV and PPB for wheezing or asthma. Fifth, I evaluated the association between the air pollution (annual-fine-particulatematter, PM2.5; nitrogen-dioxide, NO2) and greenspace (normalised-difference-vegetationindex, NDVI) and virus detections and wheeze. Increase in greenspace was associated with fewer weeks of any virus and M. catarrhalis detections in the first 3 months of life. In contrast, increases in NO2 were associated with earlier H. influenzae detections, while increases in PM2.5 were associated with earlier symptomatic HRV infections. No associations were observed with wheeze in the first 2 years of life or asthma by age 5-7 years. This Thesis found exposure to respiratory viruses/bacteria during early life may have short-term effects in addition to having symptoms of an acute respiratory infection, such as a predisposition to subsequent wheezing episodes, and longer-term effects on respiratory health, such as the development of asthma.