Reviews and feature articleDo early-life viral infections cause asthma?
Section snippets
What have we learned from the epidemiologists?
The link between viral respiratory infections in early life and subsequent childhood asthma has been the subject of much study and debate for decades. Although much of the earlier literature centered on the link between hospitalization for acute viral bronchiolitis, most commonly because of infection with the respiratory syncytial virus (RSV), recent investigations into wheezing in childhood have included more comprehensive viral assessments using modern molecular techniques in community-based
Susceptible host, virus-induced damage, or both?
Cogent arguments can, and have been, mounted for the association between early-life viral respiratory infections and childhood asthma being caused by the virus unmasking a susceptible host, or the virus causing damage to the airways that induces remodeling and results in asthma (see review5). In physiological terms, the presence of wheeze simply implies the presence of flow limitation during expiration. Wheeze can result from small airways (eg, resulting from adverse in utero exposures that
Does the response to a respiratory viral infection differ in those with asthma?
When respiratory viruses enter the lower airway, they infect bronchial epithelial cells (BECs) triggering an antiviral response aimed at containing and eliminating the infection. Infected BECs secrete a variety of products, including IFNs and proinflammatory cytokines such as IL-8. Recent reports demonstrated that the type III IFN, IFN-λ, is the major interferon secreted by infected BECs, followed by the type I IFN, IFN-β.16 These IFNs induce the BEC to undergo apoptosis, thus limiting viral
Can the nexus among viral respiratory infections, atopy, and asthma be broken?
A key component in developing therapeutic options to prevent the development of asthma is to be able to identify those children who are truly at high risk.4 Clearly every child who develops a wLRI in early life is not at risk of childhood asthma. As is clear from the majority of the epidemiologic literature, wheeze is used both as an indication of LRI and as an indication of developing asthma. However, as outlined, wheeze is a physiological phenomenon and gives no clue to the cause of the
References (20)
- et al.
Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study
Lancet
(2008) - et al.
Early identification of atopy in the prediction of persistent asthma in children
Lancet
(2008) - et al.
Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma
J Allergy Clin Immunol
(2007) - et al.
Contemporaneous maturation of immunologic and respiratory functions during early childhood: implications for development of asthma prevention strategies
J Allergy Clin Immunol
(2005) - et al.
Epigenetic regulation of airway inflammation
Curr Opin Immunol
(2007) The connection between early life wheezing and subsequent asthma: the viral march
Allergol Immunopathol (Madr)
(2009)- et al.
Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7
Am J Respir Crit Care Med
(2000) - et al.
Respiratory viruses in childhood asthma
Curr Opin Allergy Clin Immunol
(2007) Rhinovirus and the initiation of asthma
Curr Opin Allergy Clin Immunol
(2009)- et al.
Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children
Am J Respir Crit Care Med
(2008)
Cited by (116)
Which Wheezing Preschoolers Should be Treated for Asthma?
2021, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :Asthma predictive indices have been developed from several risk factors described in cohort studies that include early sensitization to food or aeroallergens, parental asthma, atopic dermatitis, male sex, peripheral blood eosinophilia at 9 months, lower early-life lung function, increased airway responsiveness, and a history of wheezing with lower respiratory tract infections.4,33-38 Significant risk factors that are common across multiple cohort studies are atopic disease,4,36-39 viral infections, especially with RV,40-43 frequent wheeze,4,44,45 and decreased lung function.4,36,38,39,46 Furthermore, a cluster analysis of European preschool-age children described a severe, persistent asthma phenotype by the type and severity of allergic sensitization, severity of wheezing episodes and triggers for wheezing in the preschool years, and response to medication.47
Recurrent Wheeze of Early Childhood
2021, Encyclopedia of Respiratory Medicine, Second EditionThe Association of Early Life Viral Respiratory Illness and Atopy on Asthma in Children: Systematic Review and Meta-Analysis
2020, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :Multiple interconnected gene-environmental and epigenetic risk factors are implicated in its causation.6-11 The “two-hit hypothesis” suggests that atopy and viral respiratory infections interact in asthma development.4,12 These factors are both common and have opportunities to exert effects on immature and developing respiratory systems.13-15
Wheezing in children: Approaches to diagnosis and management
2019, International Journal of Pediatrics and Adolescent MedicineChildhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization
2019, Immunology and Allergy Clinics of North America
Supported by grants from the National Health and Medical Research Council, Australia.
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.