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.

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.

Informations de copyright

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Déclaration de conflit d'intérêts

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.