Infant viral respiratory infection nasal immune-response patterns and their association with subsequent childhood recurrent wheeze

Kedir N. Turi, Jyoti Shankar, Larry J. Anderson, Devi Rajan, Kelsey Gaston, Tebeb Gebretsadik, Suman R. Das, Cosby Stone, Emma K. Larkin, Christian Rosas-Salazar, Steven M. Brunwasser, Martin L. Moore, R. Stokes Peebles, Tina V. Hartert

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Rationale: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection. Objectives: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze. Methods: A birth cohort of term healthy infants born June to December were recruited and followed to capture the first infant RSV infection. Nasal wash samples were collected during acute respiratory infection, viruses were identified by RT-PCR, and immune-response analytes were assayed using a multianalyte beadbased panel. Immune-response clusters were identified using machine learning, and association with recurrent wheeze at age 1 and 2 years was assessed using logistic regression. Measurements and Main Results: We identified two novel and distinct immune-response clusters to RSV and human rhinovirus. In RSV-infected infants, a nasal immune-response cluster characterized by lower non-IFN antiviral immune-response mediators, and higher type-2 and type-17 cytokines was significantly associated with first and second year recurrent wheeze. In comparison, we did not observe this in infants with human rhinovirus acute respiratory infection. Based on network analysis, type-2 and type-17 cytokines were central to the immune response to RSV, whereas growth factors and chemokines were central to the immune response to human rhinovirus. Conclusions: Distinct immune-response clusters during infant RSV infection and their association with risk of recurrent wheeze provide insights into the risk factors for and mechanisms of asthma development.

Original languageEnglish (US)
Pages (from-to)1064-1073
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume198
Issue number8
DOIs
StatePublished - Oct 15 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine
  • Pulmonary and Respiratory Medicine

Fingerprint

Dive into the research topics of 'Infant viral respiratory infection nasal immune-response patterns and their association with subsequent childhood recurrent wheeze'. Together they form a unique fingerprint.

Cite this