Bronchiolitis and asthma: the next step^☆,☆☆

Asthma is one of the most common chronic conditions during childhood. The origin of asthma is not fully understood, but it is clear that it is a complex disease in which genetic mechanisms and environmental factors are involved. In this issue of Jornal de Pediatria, Brandão et al. analyzed the relationship between acute viral bronchiolitis during the first year of life and asthma at school age in a cohort of 672 children in northeastern Brazil.¹ Acute viral bronchiolitis was defined according to the American Academy of Pediatrics (AAP) guidelines, basically requiring a combination of upper and lower respiratory symptoms in the first year of life. Even after adjusting for potential confounders, including family atopy or cigarette smoke exposure, bronchiolitis during the first year of life was independently associated with asthma at school age. Why is this study important? It hints to the possibility that we may be able to prevent asthma by preventing viral infection during early childhood. This possibility depends on the causal relationship between bronchiolitis and subsequent asthma. For rhinovirus bronchiolitis, the link is strong, but epidemiological studies suggest rhinovirus bronchiolitis "reveals" asthma rather than causing it.^2,3 For respiratory syncytial virus (RSV), the link is less strong, but the association might well be causal. RSV infection causes a robust neutrophilic airway inflammation, which may cause persistent changes to the airways,^4,5 resulting in chronic airway disease without causing allergic sensitization. In line with this hypothesis, a previous birth cohort study by Renato Stein demonstrated that RSV does not add to the risk of allergic sensitization.⁶ Causality was suggested by a complex longitudinal study by Wu et al. showing that the time gap between time of birth and the peak of the RSV season determines the risk of asthma at school age.⁷ The most convincing evidence is supposed to come from RSV prevention trials. For RSV infection, most trials have indicated that RSV prevention decreases the risk of subsequent wheeze,^8-10 although this could not be confirmed in a recent trial.¹¹ The results of these trials should be considered with caution, as all of them where performed in special populations, leaving the possibility that the direction or the size of the long-term effect of RSV on asthma is different in the normal population. Maternal or infant vaccination against influenza is one of the potential interventions to be considered. More important, probably, are the currently developed RSV vaccines.¹² Several companies have now entered the clinical development stage of their RSV vaccines. A nanoparticle-based vaccine for maternal vaccination has already entered phase III. This vaccine is being developed with the support of the Bill and Melinda Gates Foundation and is intended to be affordable, therefore it would be available in high as well as low- and middle-income countries. The clinical RSV vaccine programs of other large companies follow rapidly, so it appears to a matter of time before we have an RSV vaccine. These upcoming RSV prevention trials in the normal population will address the causal link between RSV and asthma, and show the potential for primary asthma prevention. The clinical development of all RSV vaccines is supported by studies such as that by Brandão et al., which show that prevention of acute viral bronchiolitis not only decreases the risk of a life-threatening acute disease, but may also impact on the child's lung health throughout childhood and thereafter.

• ☆
  Please cite this article as: Bont L. Bronchiolitis and asthma: the next step. J Pediatr (Rio J). 2017;93:209-10.
• ☆☆
  See paper by Brandão et al. in pages 223-9.

References

• ¹
  Brandão HV, Vieira GO, Vieira TO, Cruz ÁA, Guimarães AC, Teles C, et al. Acute viral bronchiolitis and risk of asthma in schoolchildren: analysis of a Brazilian newborn cohort. J Pediatr (Rio J). 2017;93:223-9.
• ²
  Jackson DJ, Evans MD, Gangnon RE, Tisler CJ, Pappas TE, Lee WM, et al. Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life. Am J Respir Crit Care Med. 2012;185:281-5.
• ³
  Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178:667-72.
• ⁴
  Geerdink RJ, Pillay J, Meyaard L, Bont L. Neutrophils in respiratory syncytial virus infection: a target for asthma prevention. J Allergy Clin Immunol. 2015;136:838-47.
• ⁵
  Funchal GA, Jaeger N, Czepielewski RS, Machado MS, Muraro SP, Stein RT, et al. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils. PLoS One. 2015;10:e0124082.
• ⁶
  Stein RT, Holberg CJ, Sherrill D, Wright AL, Morgan WJ, Taussig L, et al. Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study. Am J Epidemiol. 1999;149:1030-7.
• ⁷
  Wu P, Dupont WD, Griffin MR, Carroll KN, Mitchel EF, Gebretsadik T, et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am J Respir Crit Care Med. 2008;178:1123-9.
• ⁸
  Simões EA, Carbonell-Estrany X, Rieger CH, Mitchell I, Fredrick L, Groothuis JR, et al. The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children. J Allergy Clin Immunol. 2010;126:256-62.
• ⁹
  Yoshihara S, Kusuda S, Mochizuki H, Okada K, Nishima S, Simões EA, et al. Effect of palivizumab prophylaxis on subsequent recurrent wheezing in preterm infants. Pediatrics. 2013;132:811-8.
• ¹⁰
  Blanken MO, Rovers MM, Molenaar JM, Winkler-Seinstra PL, Meijer A, Kimpen JL, et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med. 2013;368:1791-9.
• ¹¹
  O'Brien KL, Chandran A, Weatherholtz R, Jafri HS, Griffin MP, Bellamy T, et al. Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: a phase 3 randomised double-blind placebo-controlled trial. Lancet Infect Dis. 2015;15:1398-408.
• ¹²
  Mazur NI, Martinón-Torres F, Baraldi E, Fauroux B, Greenough A, Heikkinen T, et al. Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet Respir Med. 2015;3:888-900.

Publication Dates

• Publication in this collection
  May-Jun 2017