A significant portion of full-term healthy babies, ranging from one-quarter to one-half, encounter respiratory syncytial virus (RSV) infection during their first year of life. Among these, approximately 2% to 3% develop small airway bronchiolitis and lower respiratory tract infections severe enough to necessitate hospital admission.
Research drawn from large-scale population studies, bolstered by experimental evidence from mouse models, underscores RSV as a modifiable risk factor that can be prevented to potentially lower asthma incidence.
Heightened Asthma Vulnerability in Infants with Parental Asthma and RSV Hospitalization
Babies who have parents with asthma and who experience hospitalization due to RSV bronchiolitis face a markedly elevated chance of developing asthma later in childhood, according to findings from an extensive population-based investigation.
Specifically, hospitalization for RSV bronchiolitis within the initial six months of life independently triples the cumulative likelihood of receiving an asthma diagnosis (HR 3.32, 95% CI 3.21-3.43). In comparison, infants born to mothers with asthma but without any RSV-related hospital stay see their risk roughly doubled (HR 2.06, 95% CI 2.01-2.10), while those born to fathers with asthma experience a similar but slightly lower increase (HR 1.71, 95% CI 1.67-1.76). These insights were shared by Bart N. Lambrecht, MD, PhD, from Ghent University in Belgium, along with his research team.
The most pronounced risk emerges in children who are both hospitalized for RSV bronchiolitis and have a parent with asthma—reaching HR 5.38 (95% CI 4.88-5.93) for those with asthmatic mothers and HR 4.73 (95% CI 4.19-5.34) for those with asthmatic fathers—when benchmarked against children without RSV exposure and born to parents free of asthma.
Investigators detailed these observations in a prominent scientific publication, highlighting how such combined factors synergize to amplify asthma susceptibility.
Mechanistic Insights from Animal Models Point to Preventability
Complementary analyses using mouse models, as outlined in the study, indicate that RSV infection may represent a preventable contributor to asthma development. The researchers explained that a specific process involving antibody-enhanced uptake of allergens, triggered by viral infection, elucidates the convergence of two major asthma risk elements—familial predisposition and early viral exposure—ultimately fostering heightened type 2 immune responses and asthma onset in vulnerable newborns.
Epidemiological patterns reveal that 25% to 50% of term-born healthy infants contract RSV within their first year, with 2-3% progressing to bronchiolitis and lower respiratory infections demanding inpatient care.
Notably, the data revealed that even infants lacking a family history of asthma exhibit a substantially greater risk of asthma following hospitalization for human RSV (hRSV). This observation, as emphasized by Lambrecht and co-authors, disputes the conventional view that RSV hospitalizations and subsequent asthma are confined to children with underlying genetic vulnerabilities.
Comprehensive Data from Danish National Registries
To conduct this robust analysis, the study team leveraged the Danish National Patient Registry alongside other nationwide databases, pinpointing almost 25,000 infants aged 6 months or younger admitted for RSV between 1994 and 2018.
These comprehensive records also tracked ongoing specialized medical interventions for asthma in both parents and children, employing prescriptions for inhalers and nasal corticosteroids as indicators of allergic rhinitis. Follow-up for asthma manifestation in the children extended up to 24 years.
Prior longitudinal cohort research has similarly associated parental asthma with increased severity of bronchiolitis in offspring during upper respiratory infections, especially those caused by rhinovirus. Consequently, RSV hospitalization in a child may serve as an indicator of broader asthma predisposition, according to the Ghent University team.
Statistical Significance of Gene-Environment Interactions
Statistical evaluations confirmed highly significant interactions (P < 0.05) between RSV bronchiolitis hospitalization and parental asthma for both maternal and paternal cases, as well as between RSV events and maternal allergic rhinitis. Even after incorporating interaction terms to account for these dynamics alongside parental asthma or rhinitis status, the core analytical results held firm.
Mouse Model Evidence Supports Causal Pathways
In pursuit of establishing causal links, the researchers employed a mouse model mimicking RSV via infection with pneumovirus PVM, a close viral relative. Offspring of asthmatic mother mice—and to some extent those from asthmatic father mice—displayed exceptionally intense type 2 inflammatory responses post early-life viral challenge. This severity stemmed from maternal transfer of allergen-specific antibodies that adhered to lung dendritic cells stimulated by the virus.
Such binding facilitated enhanced allergen processing by dendritic cells, triggering TH2 cell activation and precipitating asthma-like symptoms, as described by Lambrecht and colleagues. Notably, administration of anti-RSV antibodies to pregnant or nursing mother mice prevented the emergence of type 2 immunity in their newborns, reinforcing RSV as a targetable risk factor for asthma prevention.
Primarily, these maternal allergen-specific IgG antibodies are transmitted through breast milk, though human cord blood transfer is also possible. The team posited that paternal contributions to risk might involve various genetic elements influencing postnatal lung maturation, immune regulation, and epithelial barrier strength—factors potentially overlapping with maternal asthma transmission pathways.
Study Limitations and Broader Implications
Among the constraints acknowledged by Lambrecht’s group was their inability to ascertain if parental genetic profiles prompt early allergen-specific antibody generation in infants. Additionally, the reliance on hospital-diagnosed asthma and RSV cases introduced potential under-detection of milder instances managed solely in primary care settings.
They further reflected that while severe bronchiolitis mandating hospitalization was long viewed as the key asthma precursor, contemporary surveillance studies detecting hRSV in newborn cohorts imply that even milder infections may elevate asthma risk. Thus, their findings likely represent a conservative estimate of the full asthma burden attributable to hRSV.
