The relationship between RSV bronchiolitis and recurrent wheeze: The chicken and the egg

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Abstract

Respiratory syncytial virus bronchiolitis is the most frequent cause of infant hospitalization. RSV bronchiolitis is often followed by recurrent episodes of wheeze. Pathogenesis of RSV bronchiolitis as well as post-bronchiolitis wheeze are incompletely understood. The aim of this review is to provide a brief overview of our current understanding of the complex pathogenesis of RSV bronchiolitis and post-bronchiolitis wheeze. Two non-exclusive hypotheses exist, which are paraphrased for this review as “the chicken and the egg”. First, we reviewed the pre-existent genetic, pulmonary and immunological mechanisms of RSV bronchiolitis and post-bronchiolitis wheeze. Second, RSV as the causative virus of long-term airway morbidiy is reviewed. Clearly, RSV infection is capable of causing direct damage to the airways and/or inducing long-term inappropriate immune responses to respiratory viruses or aero-allergens. It is concluded that intervention trials aimed at preventing RSV infections are required to establish the relative contribution of both RSV-induced and pre-existent mechanisms to the development of long-term airway disease following RSV bronchiolitis.

Introduction

Respiratory syncytial virus bronchiolitis is the most common cause of hospitalization during infancy. In the general population 2% of all children are admitted for RSV bronchiolitis during the first year of life [1]. In preterm children with chronic lung disease, the risk of hospitalization for RSV infection may be as high as 33% [2]. Disease during RSV bronchiolitis is caused by complex mechanisms. Virus-induced cytopathology, virus-induced immunopathology and pre-existent susceptibility factors all contribute to symptoms observed during RSV bronchiolitis. RSV bronchiolitis is often followed by recurrent episodes of wheeze or post-bronchiolitis wheeze (PBW) [3]. The possible relationship between RSV and post-bronchiolitis wheeze is often described as a “chicken or egg” phenomenon. On one hand, RSV infection could be the cause of PBW by affecting airway structure and function or by inducing a long-term aberrant immune response to common respiratory viruses or aero-allergens. On the other hand, RSV bronchiolitis may be the first indication of long-term airway morbidity in which host susceptibility factors determine the risk of both RSV bronchiolitis and recurrent wheeze. The aim of this review is to provide a brief overview of our current understanding of the complex pathogenesis of RSV bronchiolitis and PBW.

Section snippets

Epidemiologic studies

A number of retrospective studies since the 1970s have described a clear association between RSV bronchiolitis and increased risk for subsequent wheezing [4], [5]. Because of the retrospective methodology of those initial studies, several authors raised questions about the significance of this association. However, in the last two decades a number of prospective studies conducted in different parts of the world and including children with different genetic backgrounds have confirmed a strong

Genetic susceptibility

The Danish national birth cohort study has attempted to define to what extent the risk of hospitalization for RSV bronchiolitis during the first year of life is as explained by genetic variation [13]. In 12,346 homozygous and heterozygous twins, the concordance rate for hospitalization for RSV infection was 0.66 and 0.53, respectively. It was calculated that the heritability of RSV bronchiolitis is 16%. During the last decade genetic studies have evolved and demonstrated the existence of

RSV as the cause of long-term airway morbidity

In addition to all the different factors (genetic, pulmonary, cardiac and immunologic) that are associated with increased susceptibility to develop severe RSV bronchiolitis, it is thought that the virus itself has unique characteristics that play a significant role in its ability to cause (or to be associated with) long-term pulmonary sequelae. Although the epidemiologic studies demonstrated a strong association between RSV bronchiolitis and PBW, those observational studies do not allow

Conclusion

Numerous epidemiologic studies have demonstrated a strong association between RSV bronchiolitis early in life and the development of post-bronchiolitis wheeze (PBW). The mechanisms responsible for increased susceptibility to develop severe RSV bronchiolitis are complex and multifactorial. Studies have confirmed that different genetic, pulmonary, cardiac and immunological factors influence the risk for severe bronchiolitis and PBW. In addition, experimental studies showed that the virus itself

Conflict of interest

Both authors received speaker's fees from Abbott.

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