Short summary

It is well known that children hospitalized with RSV infection have a significantly increased risk of later developing asthma, but less is known about respiratory infection with adenovirus (AV) is also associated with increased incidence of chronic lung disease later. With this study, we want to clarify whether such an association exists, as we will also investigate whether the association is weaker or stronger than the association between hospitalization with RSV and asthma.

Rationale

Metaanalysis showed that infection and hospitalization with AV was associated with sequelae in more than half of the children, and other studies have found an increased risk of both bronchiectasiae and diffuse lung disease after AV infection. In this study we aim to determine whether respiratory tract infection with AV is associated with later asthma and other chronic lung disease. We will furthermore compare this risk with the risk of similar diseases in individuals hospitalized with RSV during childhood.

Description of the cohort

Cases: Children infected with AV and RSV aged 0 - 35 months will be identified from the Department of Virology, Statens Serum Institut and from the Department of Microbiology, Slagelse Hospital. Exposure: Microbiologically proven infection with AV or RSV in children aged of 0 - 35 months during the inclusion period from 01.01.2000 to 31.12.2005 Outcome: Discharge diagnoses or outpatient diagnoses of asthma (DJ45:0 - 9 og DJ46.0), bronkieektasiae (DJ47.9) and diffuse lung disease (DJ84.0 - 9) until 31.12.2020 Adjustments: Analyses will be adjusted for mode of birth (vaginally vs. sectio cesarean (KMCA10D, KMCA10E, KMCA00, KMCA10A, KMCA10B, KMCA12, KMCA33, KMCA20)), Gestational age at birth, birth weight, Small for gestational age, appropriate for gestational age, large for gestational age and Apgar score after 5 minutes. Follow up: All children will be followed until end of follow up on 31.12.2020.

Data and biological material

Data: children diagnosed with respiratory tract infection with AV or RSV will be traced via the Department of Virology, Statens Seruminstitut and The Department of Clinical Microbiology, Slagelse Hospital. A control group matched on date of birth will furthermore be included in the study. By using the children`s unique CPR they will be linked with the following databases, from which data on outcome variables and confounders will be drawn: 1. The National Patient registry, which holds data on all diagnoses on in- and outpatients at Danish hospitals 2. The Danish Medical Birth registry, which holds data on birth mode, gestational age, birth weight, birth length and Apgar score 3. The Danish National Prescription Registry, which holds data on prescriptions redeemed in Denmark

Sample size: The sample size is limited by the number of cases with diagnosed infection with AV (n = 71). Assuming that 67 of these can be included in the study, we will have a power of 80% to detect a hazard ratio of 3 with a significance level of 0.05 if the control group comprises 155 individuals. However, to make sure we intend to include 5 controls per case.

Collaborating researchers and departments

Department of Virology, Statens Seruminstitut

Department of Clinical Microbiology, Slagelse Hospital

OPEN OUH

Publications associated with the project

Fischer GB, Sarria EE, Mattiello R, Mocelin HT, Castro-Rodriguez JA. Post infectious bronchiolitis obliterans in children. Paediatr Respir Rev. 2010 Dec;11(4):233-9. doi: 10.1016/j.prrv.2010.07.005. Epub 2010 Aug 19. PMID: 21109182.

Rosas-Salazar C, Chirkova T, Gebretsadik T, Chappell JD, Peebles RS Jr, Dupont WD, Jadhao SJ, Gergen PJ, Anderson LJ, Hartert TV. Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population-based, prospective birth cohort study. Lancet. 2023 May 20;401(10389):1669-1680.

Nguyen-Van-Tam J, Wyffels V, Smulders M, Mazumder D, Tyagi R, Gupta N, Gavart S, Fleischhackl R. Cumulative incidence of post-infection asthma or wheezing among young children clinically diagnosed with respiratory syncytial virus infection in the United States: A retrospective database analysis. Influenza Other Respir Viruses. 2020 Nov;14(6):730-738. doi: 10.1111/irv.12770. Epub 2020 Jun 12. PMID: 32533658; PMCID: PMC7578296.