Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life

Shabir A. Madhi; Ana Ceballos; Luis Cousin; Joseph B. Domachowske; Joanne M. Langley; Emily Lu; Thanyawee Puthanakit; Mika Rämet; Amy Tan; Khalequ Zaman; Bruno Anspach; Agustin Bueso; Elisa Cinconze; Jo Ann Colas; Ulises D'andrea; Ilse Dieussaert; Janet A. Englund; Sanjay Gandhi; Lisa Jose; Hanna Karhusaari; Joon Hyung Kim; Nicola P. Klein; Outi Laajalahti; Runa Mithani; Martin O.C. Ota; Mauricio Pinto; Peter Silas; Sonia K. Stoszek; Auchara Tangsathapornpong; Jamaree Teeratakulpisarn; Miia Virta; Rachel A. Cohen

doi:10.1097/INF.0000000000004447

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life

Shabir A. Madhi
, Ana Ceballos
, Luis Cousin
, Joseph B. Domachowske
, Joanne M. Langley
, Emily Lu
, Thanyawee Puthanakit
, Mika Rämet
, Amy Tan
, Khalequ Zaman
, Bruno Anspach
, Agustin Bueso
, Elisa Cinconze
, Jo Ann Colas
, Ulises D'andrea
, Ilse Dieussaert
, Janet A. Englund
, Sanjay Gandhi
, Lisa Jose
, Hanna Karhusaari

Joon Hyung Kim, Nicola P. Klein, Outi Laajalahti, Runa Mithani, Martin O.C. Ota, Mauricio Pinto, Peter Silas, Sonia K. Stoszek, Auchara Tangsathapornpong, Jamaree Teeratakulpisarn, Miia Virta, Rachel A. Cohen^*

^*Corresponding author for this work

Biosciences

Research output: Contribution to journal › Article › Scientific › peer-review

4 Citations (Scopus)

1 Downloads (Pure)

Abstract

Background: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). Methods: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. Results: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). Conclusions: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Original language	English
Pages (from-to)	379-386
Journal	Pediatric Infectious Disease Journal
Volume	44
Issue number	5
Early online date	2024
DOIs	https://doi.org/10.1097/INF.0000000000004447
Publication status	Published - 2025
Publication type	A1 Journal article-refereed

Funding

This work was supported by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA covered all costs associated with the development and publishing of the present manuscript. E.L., A.T., B.A., E.C., J.A.C., I.D., S.G., J.H.K., R.M., M.O.O., S.K.S. and R.A.C. are/were employees of GSK. E.L., B.A., I.D., S.G., J.H.K., S.K.S. and R.A.C. hold/held GSK shares. S.A.M. declares receiving GSK funding to his institution for the conduct of the study, grants to his institution from Bill & Melinda Gates Foundation, GSK, Pfizer, and MinervaX, clinical trial funding to institution from Novavax, Merck, Providence Therapeutics, Gritstone bio, and ImmunityBio, and GSK payment honoraria for lectures. He was also Chair of Data Safety Monitoring Board for PATH (rotavirus vaccine) and CAPRISA (HIV monoclonal antibody). J.M.L. received GSK funding to Dalhousie University, received grants or contracts from GSK, Pfizer, Merck, and Moderna, and consulting fees from GSK. The author declares other financial or nonfinancial interests as expert panelist for the Canadian Agency for Drugs and Technologies in Health (CADTH) review of nirsevimab. T.P. received grants from GSK. M.R. is a national coordinator and/or principal investigator for several clinical trials sponsored by GSK and other vaccine manufacturers and received grants from GSK to his institution. J.A.E. received research support to her institution from AstraZeneca, GSK, Merck, and Pfizer, and is a consultant for AstraZeneca, AbbVie, Shanghai Ark Biopharmaceutical Co., GSK, Pfizer, Sanofi Pasteur, and Shionogi. N.P.K. received research support to her institution from GSK, and grants/contracts to her institution from Pfizer, Sanofi Pasteur, Merck, and CSL Seqirus. M.P.R. received support from Demedica. SKS received funding from GSK for attending conferences. Other authors have no conflicts of interest to disclose.

Funders
GlaxoSmithKline
GSK
Pfizer
Merck Oy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

LRTI
population attributable risk
RSV
RSV sequelae
wheeze

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Microbiology (medical)
Infectious Diseases

Access to Document

10.1097/INF.0000000000004447

https://urn.fi/URN:NBN:fi:tuni-202411049807Licence: Unspecified

Cite this

Madhi, S. A., Ceballos, A., Cousin, L., Domachowske, J. B., Langley, J. M., Lu, E., Puthanakit, T., Rämet, M., Tan, A., Zaman, K., Anspach, B., Bueso, A., Cinconze, E., Colas, J. A., D'andrea, U., Dieussaert, I., Englund, J. A., Gandhi, S., Jose, L., ... Cohen, R. A. (2025). Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life. Pediatric Infectious Disease Journal, 44(5), 379-386. https://doi.org/10.1097/INF.0000000000004447

@article{d296ddf02e194c64b64cbd55b3eb9aed,

title = "Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life",

abstract = "Background: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR\%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). Methods: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR\% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. Results: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1\% vs. 13.6\%), medically-attended (30.2\% vs. 11.8\%) and recurrent wheeze outcomes (4.0\% vs. 0.6\%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR\% of 14.1\%, 12.3\% and 35.9\%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). Conclusions: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.",

keywords = "LRTI, population attributable risk, RSV, RSV sequelae, wheeze",

author = "Madhi, \{Shabir A.\} and Ana Ceballos and Luis Cousin and Domachowske, \{Joseph B.\} and Langley, \{Joanne M.\} and Emily Lu and Thanyawee Puthanakit and Mika R{\"a}met and Amy Tan and Khalequ Zaman and Bruno Anspach and Agustin Bueso and Elisa Cinconze and Colas, \{Jo Ann\} and Ulises D'andrea and Ilse Dieussaert and Englund, \{Janet A.\} and Sanjay Gandhi and Lisa Jose and Hanna Karhusaari and Kim, \{Joon Hyung\} and Klein, \{Nicola P.\} and Outi Laajalahti and Runa Mithani and Ota, \{Martin O.C.\} and Mauricio Pinto and Peter Silas and Stoszek, \{Sonia K.\} and Auchara Tangsathapornpong and Jamaree Teeratakulpisarn and Miia Virta and Cohen, \{Rachel A.\}",

year = "2025",

doi = "10.1097/INF.0000000000004447",

language = "English",

volume = "44",

pages = "379--386",

journal = "Pediatric Infectious Disease Journal",

issn = "0891-3668",

publisher = "Lippincott Williams and Wilkins",

number = "5",

}

Madhi, SA, Ceballos, A, Cousin, L, Domachowske, JB, Langley, JM, Lu, E, Puthanakit, T, Rämet, M, Tan, A, Zaman, K, Anspach, B, Bueso, A, Cinconze, E, Colas, JA, D'andrea, U, Dieussaert, I, Englund, JA, Gandhi, S, Jose, L, Karhusaari, H, Kim, JH, Klein, NP, Laajalahti, O, Mithani, R, Ota, MOC, Pinto, M, Silas, P, Stoszek, SK, Tangsathapornpong, A, Teeratakulpisarn, J, Virta, M & Cohen, RA 2025, 'Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life', Pediatric Infectious Disease Journal, vol. 44, no. 5, pp. 379-386. https://doi.org/10.1097/INF.0000000000004447

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life. / Madhi, Shabir A.; Ceballos, Ana; Cousin, Luis et al.
In: Pediatric Infectious Disease Journal, Vol. 44, No. 5, 2025, p. 379-386.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life

AU - Madhi, Shabir A.

AU - Ceballos, Ana

AU - Cousin, Luis

AU - Domachowske, Joseph B.

AU - Langley, Joanne M.

AU - Lu, Emily

AU - Puthanakit, Thanyawee

AU - Rämet, Mika

AU - Tan, Amy

AU - Zaman, Khalequ

AU - Anspach, Bruno

AU - Bueso, Agustin

AU - Cinconze, Elisa

AU - Colas, Jo Ann

AU - D'andrea, Ulises

AU - Dieussaert, Ilse

AU - Englund, Janet A.

AU - Gandhi, Sanjay

AU - Jose, Lisa

AU - Karhusaari, Hanna

AU - Kim, Joon Hyung

AU - Klein, Nicola P.

AU - Laajalahti, Outi

AU - Mithani, Runa

AU - Ota, Martin O.C.

AU - Pinto, Mauricio

AU - Silas, Peter

AU - Stoszek, Sonia K.

AU - Tangsathapornpong, Auchara

AU - Teeratakulpisarn, Jamaree

AU - Virta, Miia

AU - Cohen, Rachel A.

PY - 2025

Y1 - 2025

N2 - Background: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). Methods: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. Results: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). Conclusions: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

AB - Background: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). Methods: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. Results: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). Conclusions: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

KW - LRTI

KW - population attributable risk

KW - RSV

KW - RSV sequelae

KW - wheeze

U2 - 10.1097/INF.0000000000004447

DO - 10.1097/INF.0000000000004447

M3 - Article

C2 - 38985986

AN - SCOPUS:85198727757

SN - 0891-3668

VL - 44

SP - 379

EP - 386

JO - Pediatric Infectious Disease Journal

JF - Pediatric Infectious Disease Journal

IS - 5

ER -

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life

Abstract

Funding

UN SDGs

Keywords

Publication forum classification

ASJC Scopus subject areas

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