Asthma and lower airway disease
The causal direction in the association between respiratory syncytial virus hospitalization and asthma

https://doi.org/10.1016/j.jaci.2008.10.042Get rights and content

Background

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.

Objective

The current study examined the causal direction of the associations between RSV hospitalization and asthma in a population-based cohort of twins.

Methods

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.

Results

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.

Conclusion

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.

Section snippets

Personal identification number

A unique identification number is assigned to every Danish citizen and registered in the Danish Civil Registration System (CRS; http://www.cpr.dk). The personal identification number serves as key reference to the individual citizen in all registries and provides a simple method for linking registry information. The CRS keeps daily updated demographic information inclusive of deaths and migration on all residents in Denmark.22 To adjust the analysis, information on sex together with information

Results

Among the included infants, 4.6% (848/18,614) had an RSV-associated hospitalization within their first 5 years of life. Of the infants, 5.9% (1014/18,614) were hospitalized with asthma, 13.2% (2307/18,614) used inhaled corticosteroids at least once, and in a subgroup of these, 7.3% (1273/18,608) used inhaled corticosteroids twice during any 1 year of their first 5 years of life. The occurrence in the cohort of RSV hospitalization and asthma by sex, zygosity, and age is presented in Table I.

Discussion

We examined the risk of asthma after RSV hospitalization and the risk of RSV hospitalization after asthma in a cohort of all Danish twins born alive between 1994 and 2004 and followed from birth to 5 years of age. We found an increased risk of asthma after RSV hospitalization, in agreement with previous studies.8, 9, 10, 11, 12, 13, 28 The risk of asthma depended on the time since the RSV hospitalization, with a 6-fold to 8-fold increase the first few months but only a slight increase after 1

References (31)

  • M. Eriksson et al.

    Wheezing following lower respiratory tract infections with respiratory syncytial virus and influenza A in infancy

    Pediatr Allergy Immunol

    (2000)
  • J.A. Castro-Rodriguez et al.

    Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study

    Am J Respir Crit Care Med

    (1999)
  • J.T. McBride

    Pulmonary function changes in children after respiratory syncytial virus infection in infancy

    J Pediatr

    (1999)
  • N. Sigurs et al.

    Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13

    Am J Respir Crit Care Med

    (2005)
  • N. Sigurs et al.

    Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls

    Pediatrics

    (1995)
  • Cited by (101)

    • Nucleic Acid Sensing in Allergic Disorders

      2019, International Review of Cell and Molecular Biology
    View all citing articles on Scopus

    Supported by the Lundbeck Foundation, the Augustinus Foundation, and an unrestricted institutional grant from MedImmune.

    Disclosure of potential conflict of interest: V. Backer receives grant support from AstraZeneca, Boehringer Ingelheim, ALK-Abelló, and Novartis. H. Bisgaard has been a consultant to, has been a paid lecturer for, and holds sponsored grants from Aerocrine, AstraZeneca, Altana, GlaxoSmithKline, Merck, MedImmune, NeoLab, and Pfizer; receives grant support from Aerocrine, AstraZeneca, GlaxoSmithKline, Merck, and MedImmune; and has provided legal consultation/expert witness testimony for NeoLab. The rest of the authors have declared that they have no conflict of interest.

    View full text