Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection

The RESCEU Investigators; Xin Wang; You Li; Harish Nair; Harry Campbell

doi:10.1093/infdis/jiab308

Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection

The RESCEU Investigators, Xin Wang^*, You Li, Harish Nair, Harry Campbell

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Background. Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. Methods. We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. Results. The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6-23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1-4.9) for the first 2 years, 2.3 (95% CI, 1.6-3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2-2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0-5 months. Conclusions. We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6-23 months compared to those whose first severe RSV infection occurred at 0-6 months. This provides new evidence for further assessment of the association and RSV intervention programs.

Original language	English
Journal	Journal of Infectious Diseases
Volume	226
Pages (from-to)	S38-S44
ISSN	0022-1899
DOIs	https://doi.org/10.1093/infdis/jiab308
Publication status	Published - 1 Aug 2022
Externally published	Yes

Bibliographical note

Funding Information:
This work was funded by the Innovative Medicines Initiative 2 Joint Undertaking (Grant 116019), which in turn receives support from the European Union's Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations. The supplement is sponsored by RESCEU. The content in this article reflects only the authors' view, and the EC is not responsible for any use that may be made of the information it contains.

Funding Information:
Potential conflicts of interest. H. C. reports grants from the European Union Innovative Medicines Initiative; grants and personal fees from the World Health Organization; and grants from the Bill & Melinda Gates Foundation during the conduct of the study. H. N. reports grants from World Health Organization, grants and personal fees from Sanofi Pasteur, personal fees from Janssen, personal fees from the Bill & Melinda Gates Foundation, personal fees from Reviral, personal fees from AbbVie, and grants from the National Institute of Health Research outside the submitted work. Y. L. reports grants from the World Health Organization; and grants from Wellcome Trust outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Keywords

age at first RSV infection
asthma
severe RSV infections
time since RSV infection
wheeze

Link to document

10.1093/infdis/jiab308

Cite this

@article{2c4e281e44994838b8cbeb53eda7580c,

title = "Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection",

abstract = "Background. Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. Methods. We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. Results. The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6-23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1-4.9) for the first 2 years, 2.3 (95% CI, 1.6-3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2-2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0-5 months. Conclusions. We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6-23 months compared to those whose first severe RSV infection occurred at 0-6 months. This provides new evidence for further assessment of the association and RSV intervention programs.",

keywords = "age at first RSV infection, asthma, severe RSV infections, time since RSV infection, wheeze",

author = "{The RESCEU Investigators} and Xin Wang and You Li and Harish Nair and Harry Campbell and Reeves, {Rachel M.} and {van Wijhe}, Maarten and Fischer, {Thea K{\o}lsen} and Lone Simonsen and Ramona Trebbien and Sabine Tong and Mathieu Bangert and Clarisse Demont and Toni Lehtonen and Terho Heikkinen and Anne Teirlinck and {van Boven}, Michiel and {van der Hoek}, Wim and {van der Maas}, Nicoline and Adam Meijer and Fernandez, {Liliana Vazquez} and H{\aa}kon B{\o}as and Terese Bekkevold and Elmira Flem and Luca Stona and Irene Speltra and Carlo Giaquinto and Arnaud Cheret and Amanda Leach and Sonia Stoszek and Philippe Beutels and Louis Bont and Andrew Pollard and Peter Openshaw and Michael Abram and Kena Swanson and Brian Rosen and Eva Molero",

note = "Funding Information: This work was funded by the Innovative Medicines Initiative 2 Joint Undertaking (Grant 116019), which in turn receives support from the European Union's Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations. The supplement is sponsored by RESCEU. The content in this article reflects only the authors' view, and the EC is not responsible for any use that may be made of the information it contains. Funding Information: Potential conflicts of interest. H. C. reports grants from the European Union Innovative Medicines Initiative; grants and personal fees from the World Health Organization; and grants from the Bill & Melinda Gates Foundation during the conduct of the study. H. N. reports grants from World Health Organization, grants and personal fees from Sanofi Pasteur, personal fees from Janssen, personal fees from the Bill & Melinda Gates Foundation, personal fees from Reviral, personal fees from AbbVie, and grants from the National Institute of Health Research outside the submitted work. Y. L. reports grants from the World Health Organization; and grants from Wellcome Trust outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: {\textcopyright} The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.",

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month = aug,

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doi = "10.1093/infdis/jiab308",

language = "English",

volume = "226",

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Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection. / The RESCEU Investigators; Wang, Xin; Li, You et al.
In: Journal of Infectious Diseases, Vol. 226, 01.08.2022, p. S38-S44.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection

AU - The RESCEU Investigators

AU - Wang, Xin

AU - Li, You

AU - Nair, Harish

AU - Campbell, Harry

A2 - Reeves, Rachel M.

A2 - van Wijhe, Maarten

A2 - Fischer, Thea Kølsen

A2 - Simonsen, Lone

A2 - Trebbien, Ramona

A2 - Tong, Sabine

A2 - Bangert, Mathieu

A2 - Demont, Clarisse

A2 - Lehtonen, Toni

A2 - Heikkinen, Terho

A2 - Teirlinck, Anne

A2 - van Boven, Michiel

A2 - van der Hoek, Wim

A2 - van der Maas, Nicoline

A2 - Meijer, Adam

A2 - Fernandez, Liliana Vazquez

A2 - Bøas, Håkon

A2 - Bekkevold, Terese

A2 - Flem, Elmira

A2 - Stona, Luca

A2 - Speltra, Irene

A2 - Giaquinto, Carlo

A2 - Cheret, Arnaud

A2 - Leach, Amanda

A2 - Stoszek, Sonia

A2 - Beutels, Philippe

A2 - Bont, Louis

A2 - Pollard, Andrew

A2 - Openshaw, Peter

A2 - Abram, Michael

A2 - Swanson, Kena

A2 - Rosen, Brian

A2 - Molero, Eva

N1 - Funding Information: This work was funded by the Innovative Medicines Initiative 2 Joint Undertaking (Grant 116019), which in turn receives support from the European Union's Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations. The supplement is sponsored by RESCEU. The content in this article reflects only the authors' view, and the EC is not responsible for any use that may be made of the information it contains. Funding Information: Potential conflicts of interest. H. C. reports grants from the European Union Innovative Medicines Initiative; grants and personal fees from the World Health Organization; and grants from the Bill & Melinda Gates Foundation during the conduct of the study. H. N. reports grants from World Health Organization, grants and personal fees from Sanofi Pasteur, personal fees from Janssen, personal fees from the Bill & Melinda Gates Foundation, personal fees from Reviral, personal fees from AbbVie, and grants from the National Institute of Health Research outside the submitted work. Y. L. reports grants from the World Health Organization; and grants from Wellcome Trust outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Background. Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. Methods. We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. Results. The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6-23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1-4.9) for the first 2 years, 2.3 (95% CI, 1.6-3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2-2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0-5 months. Conclusions. We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6-23 months compared to those whose first severe RSV infection occurred at 0-6 months. This provides new evidence for further assessment of the association and RSV intervention programs.

AB - Background. Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. Methods. We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. Results. The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6-23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1-4.9) for the first 2 years, 2.3 (95% CI, 1.6-3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2-2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0-5 months. Conclusions. We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6-23 months compared to those whose first severe RSV infection occurred at 0-6 months. This provides new evidence for further assessment of the association and RSV intervention programs.

KW - age at first RSV infection

KW - asthma

KW - severe RSV infections

KW - time since RSV infection

KW - wheeze

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U2 - 10.1093/infdis/jiab308

DO - 10.1093/infdis/jiab308

M3 - Journal article

C2 - 34522963

AN - SCOPUS:85136340992

SN - 0022-1899

VL - 226

SP - S38-S44

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

ER -

Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection

Abstract

Bibliographical note

Keywords

Link to document

Other files and links

RESCEU: RESCEU - REspiratory Syncytial virus Consortium in EUrope

Cite this

Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection

Abstract

Bibliographical note

Keywords

Link to document

Other files and links

Projects

RESCEU: RESCEU - REspiratory Syncytial virus Consortium in EUrope

Cite this