The causal direction in the association between respiratory syncytial virus hospitalization and asthma

Bandim Health Project, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 02/2009; 123(1):131-137.e1. DOI: 10.1016/j.jaci.2008.10.042
Source: PubMed


Earlier studies have reported an increased risk of asthma after respiratory syncytial virus (RSV) hospitalization. Other studies found that asthmatic disposition and propensity to wheeze increase the risk of RSV hospitalization.
The current study examined the causal direction of the associations between RSV hospitalization and asthma in a population-based cohort of twins.
We conducted a prospective cohort study examining the associations between RSV hospitalization and asthma by using registry information on RSV hospitalization and asthma among 18,614 Danish twins born 1994 to 2003. The associations between RSV and asthma were examined in both directions: we examined the risk of asthma after RSV hospitalization, and the risk of RSV hospitalization in children with asthma in the same population-based cohort.
Asthma hospitalization after RSV hospitalization was increased as much as 6-fold to 8-fold during the first 2 months after RSV hospitalization but was no longer increased 1 year later. Asthma increased the risk of RSV hospitalization by 3-fold, and the risk was not time-dependent. Analyzing these associations on the basis of asthma defined from use of inhaled corticosteroid did not materially change the risk estimates.
There is a bidirectional association between severe RSV infection and asthma. Severe RSV infection is associated with a short-term increase in the risk of subsequent asthma, suggesting that RSV induce bronchial hyperresponsiveness; and asthma is associated with a long-term increased susceptibility for severe RSV disease, suggesting a host factor being responsible for the severe response to RSV infection. This suggests that severe RSV infection and asthma may share a common genetic predisposition and/or environmental exposure.

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Available from: Peter Aaby, Sep 06, 2014
    • "Thus, the association between severe RSVinfection and asthma is reciprocal [8] [9]. Despite extensive research efforts, safe and effective vaccines against RSV are currently unavailable. "
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    • "When this was done, the hypothesis that asthma causes RSV hospitalization was feasible, whilst RSV hospitalization causes asthma was rejected. A second twin study showed the effect of RSV hospitalization on asthma was only for a short time (up to 2 months after hospitalization), and subsequently the increased risk of wheezing was lost by 1 year of age [Stensballe et al. 2009b]. Lastly, a study of 37 monozygotic twins, discordant for severe RSV bronchiolitis in infancy, indicated no effect of severity of RSV infection on asthma development [Poorisrisak et al. 2010]. "
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    ABSTRACT: Viral aetiology, host susceptibility (in particular allergic predisposition and sensitization), and illness severity, timing and frequency all appear to contribute as synergistic factors to the risk of developing asthma. Experimental models have shown both innate and adaptive immune responses contribute to this risk with lung inflammatory cells showing marked differences in phenotype and function in young compared with older animals, and these differences are further enhanced following virus infection. Findings to date strongly suggest that the impact of infant and preschool viral infections on the maturing immune system and developing lung that subsequently result in an asthma phenotype occur during a critical susceptibility period, and in a genetically susceptible host. There are currently no therapeutic strategies that allow primary or secondary prevention of asthma following early life viral respiratory infections in high-risk children, thus a focus on understanding the mechanisms of progression from viral wheezing in infants and preschool children to asthma development are urgently needed. This review summarizes the data reporting the role of the two most common viruses, that is, respiratory syncytial virus and human rhinovirus, that result in asthma development, comparing risk factors for disease progression, and providing insight into strategies that might be adopted to prevent asthma development.
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    • "Given conflicting findings in the literature, with different studies and study types (e.g., twin studies) coming to different conclusions [28,34,35], a definitive explanation of the relationship of RSV infection to the development of asthma remains elusive [36]. What is clear is that future studies need to include more detail with respect to direct capture of genetic information. "
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    ABSTRACT: Background Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing. Methods A retrospective cohort study examined children born at ≥32 weeks gestation between 1996–2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. Results The study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32–33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03–1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49–4.50). Conclusions Laboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.
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