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Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8+ T cells expressing TNFα and IFNγ

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Abstract

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5–14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8+ cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO2 nadir was associated with an increased ascending aorta peak systolic velocity (r = − 0.48, p < 0.05). As well, both a lower SaO2 nadir and an increased ascending aorta peak systolic velocity were associated with higher SDSC Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep subscale scores but not the polysomnographic-derived Obstructive Apnea–Hypopnea Index. The finding of elevated ascending aortic peak systolic blood flow velocity and its association with increased inflammatory markers suggests that the profile of cardiovascular changes noted in adult SDB may also occur in children with mild SDB.

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Acknowledgements

We would like to thank the staff of the MRI Unit of the Royal Adelaide Hospital and Sleep Disorders Unit, Women’s and Children’s Hospital, Adelaide. Financial support for this study was provided by National Health and Medical Council of Australia (Project No. 453637).

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Author notes

  1. Anna Kontos and Scott Willoughby contributed equally.

Authors and Affiliations

  1. Robinson Research Institute, University of Adelaide, 3rd Floor Norwich Building, 55 King William Street, North Adelaide, 5006, Australia

    Anna Kontos & Declan Kennedy

  2. Discipline of Paediatrics, School of Medicine, University of Adelaide, Adelaide, Australia

    Anna Kontos & Declan Kennedy

  3. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia

    Scott Willoughby & Matthew Worthley

  4. Research Branch, University of Adelaide, Adelaide, Australia

    Cameron van den Heuvel

  5. Department of Respiratory and Sleep Medicine, Women’s and Children’s Hospital, Adelaide, Australia

    Declan Kennedy, James Martin & Yvonne Pamula

  6. Lung Research, Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia

    Greg Hodge

  7. Cardiology Department, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia

    Matthew Worthley, Adam Nelson & Karen Teo

  8. Discipline of Medicine, University of Adelaide, Adelaide, Australia

    Matthew Worthley, Adam Nelson & Karen Teo

  9. School of Biological Sciences, University of Adelaide, Adelaide, Australia

    Adelene Kaihui Chin

  10. School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, Australia

    Mathias Baumert

  11. School of Psychology, Social Work and Social Policy, University of South Australia, Adelaide, Australia

    Kurt Lushington

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  1. Anna Kontos
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Contributions

Study design: CH, SW, GH, JM and DK. Data collection: Cd, YP, SW, MW, KT, AN, GH and A. AK, SW, GH, CH, AKC and KL conducted the data analysis and interpretation of data. All authors were involved in the preparation of the manuscript.

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Correspondence to Anna Kontos.

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Conflict of interest

Dr. Anna Kontos was supported by an Australian Post-graduate Scholarship through the University of Adelaide. Dr. Scott Willoughby was supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC) of Australia. A/Prof. Matthew Worthley has a SA Health Early to Mid-Career Practitioner Fellowship. The other authors have indicated no conflict of interest.

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Kontos, A., Willoughby, S., van den Heuvel, C. et al. Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8+ T cells expressing TNFα and IFNγ. Heart Vessels 33, 537–548 (2018). https://doi.org/10.1007/s00380-017-1090-4

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