Two distinct infant immune-response clusters in response to infant respiratory syncytial virus (RSV) infection have been identified, one of which is associated with an elevated risk for subsequent wheeze in childhood, according to the results of a prospective birth cohort study conducted in a subset of the ongoing Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) study.

The findings of the analysis were published in the American Journal of Respiratory and Critical Care Medicine.

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The investigators sought to understand how RSV might contribute to later childhood asthma and wheeze by identifying infant immune-response patterns to RSV infection (termed “the viral-nasal immune-response pattern”) at the site of infection, in order to compare it with human rhinovirus (HRV) — another common infant respiratory virus and risk factor for asthma. The objective of the study was to establish pathways via which RSV immunomodulation might be associated with the development of childhood recurrent wheeze.

A birth cohort comprised full-term healthy infants born between June and December was recruited and followed to capture the first infant RSV infection. Nasal wash samples were obtained during acute respiratory infection, viruses were identified with the use of real-time polymerase chain reaction (PCR), and immune-response analytes were assayed.

Nasal samples from 193 infants (a total of 232 samples, which included repeated infections) who were either RSV PCR-positive (108 first and 4 second infections) or HRV PCR-positive (102 first and 18 second infections) were profiled. For each virus —RSV and HRV — the researchers used only the samples from the first infection.

The researchers identified 2 novel and distinct immune-response clusters to RSV and HRV. Of the infants infected with RSV, a nasal immune-response pattern characterized by lower non-interferon antiviral immune response mediators and higher type 2 and type 17 cytokines was significantly associated with recurrent wheeze at 1 year (adjusted odds ratio [aOR], 4.78; 95% CI, 1.73-13.24) and 2 years (aOR, 2.83; 95% CI, 1.08-7.44). This same cluster was not observed in infants infected with HRV.

Network analysis demonstrated that type 2 and type 17 cytokines were key to the immune response to RSV, whereas growth factors and chemokines were key to the immune response to HRV.

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The investigators concluded that distinct immune-response patterns during RSV infection in infancy and their association with the risk for recurrent wheeze may offer insight into the risk factors for and mechanisms involved in the development of asthma.


Turi KN, Shankar J, Anderson LJ, et al. Infant viral respiratory infection nasal-immune-response patterns and their association with subsequent childhood recurrent wheeze [published online May 7, 2018]. Am J Respir Crit Care Med. doi:10.1164/rccm.201711-2348OC