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

doi:https://doi.org/10.1164/rccm.201711-2348OC

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 journal › Article › peer-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 language	American English
Pages (from-to)	1064-1073
Number of pages	10
Journal	American journal of respiratory and critical care medicine
Volume	198
Issue number	8
DOIs	https://doi.org/10.1164/rccm.201711-2348OC
State	Published - Oct 15 2018
Externally published	Yes

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine

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https://doi.org/10.1164/rccm.201711-2348OC

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Turi, K. N., Shankar, J., Anderson, L. J., Rajan, D., Gaston, K., Gebretsadik, T., Das, S. R., Stone, C., Larkin, E. K., Rosas-Salazar, C., Brunwasser, S. M., Moore, M. L., Peebles, R. S., & Hartert, T. V. (2018). Infant viral respiratory infection nasal immune-response patterns and their association with subsequent childhood recurrent wheeze. American journal of respiratory and critical care medicine, 198(8), 1064-1073. https://doi.org/10.1164/rccm.201711-2348OC

@article{6f2601c45de24547803b9dad878bad13,

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

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.",

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

note = "Funding Information: Supported by the NIH (U19AI95227, K24 AI 77930, R21HD087864, and T32HL087738). Publisher Copyright: {\textcopyright} 2018 by the American Thoracic Society.",

year = "2018",

month = oct,

day = "15",

doi = "https://doi.org/10.1164/rccm.201711-2348OC",

language = "American English",

volume = "198",

pages = "1064--1073",

journal = "American journal of respiratory and critical care medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "8",

}

Turi, KN, Shankar, J, Anderson, LJ, Rajan, D, Gaston, K, Gebretsadik, T, Das, SR, Stone, C, Larkin, EK, Rosas-Salazar, C, Brunwasser, SM, Moore, ML, Peebles, RS & Hartert, TV 2018, 'Infant viral respiratory infection nasal immune-response patterns and their association with subsequent childhood recurrent wheeze', American journal of respiratory and critical care medicine, vol. 198, no. 8, pp. 1064-1073. https://doi.org/10.1164/rccm.201711-2348OC

TY - JOUR

T1 - Infant viral respiratory infection nasal immune-response patterns and their association with subsequent childhood recurrent wheeze

AU - Turi, Kedir N.

AU - Shankar, Jyoti

AU - Anderson, Larry J.

AU - Rajan, Devi

AU - Gaston, Kelsey

AU - Gebretsadik, Tebeb

AU - Das, Suman R.

AU - Stone, Cosby

AU - Larkin, Emma K.

AU - Rosas-Salazar, Christian

AU - Brunwasser, Steven M.

AU - Moore, Martin L.

AU - Peebles, R. Stokes

AU - Hartert, Tina V.

PY - 2018/10/15

Y1 - 2018/10/15

N2 - 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.

AB - 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.

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U2 - https://doi.org/10.1164/rccm.201711-2348OC

DO - https://doi.org/10.1164/rccm.201711-2348OC

M3 - Article

C2 - 29733679

SN - 1073-449X

VL - 198

SP - 1064

EP - 1073

JO - American journal of respiratory and critical care medicine

JF - American journal of respiratory and critical care medicine

IS - 8

ER -

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

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