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Biochemical markers of cardiac dysfunction in children with obstructive sleep apnoea (OSA)

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Objectives

We explored relationships between biochemical markers and cardiac responses of children with and without obstructive sleep apnoea (OSA) during exercise. We hypothesised that serum markers of sympathetic nervous system activity and low-grade inflammation would correlate with cardiac responses to exercise in children with or without OSA.

Methodology

The study included 40 of 71 children with previously characterised responses to cardiopulmonary exercise testing. Measures included serum cytokine levels using a multiplex bead-based assay (interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α and IFN-γ). Serum amyloid A (SAA) was quantified by nephelometry, and metanephrine/normetanephrine levels were measured by liquid chromatography, mass-spectroscopy. Comparisons were made between children with and without OSA, and with and without obesity. Relationships between biomarkers and various cardiac parameters were explored by linear regression.

Results

Amongst the 40 children in this study, OSA was present in 23. Compared to the 17 children without OSA, those with OSA had higher resting serum IL-6 levels compared to those without (median 3.22 pg/ml vs. 2.31, p < 0.05). Regarding correlations with cardiac function after adjusting for OSA, IL-8 negatively correlated to heart rate (HR) response following exercise (p = 0.03) and IFN-γ negatively correlated with Stroke Volume Index (SVI) (p = 0.03). Both metanephrine and normetanephrine levels positively correlated with SVI (p = 0.04, p = 0.047; respectively) and QI (p = 0.04, p = 0.04; respectively) during exercise when adjusting for OSA.

Conclusions

Children with OSA have raised morning levels of serum IL-6. Separately, higher levels of IFN-γ and IL-8 and lower levels of metanephrine and normetanephrine related to poorer cardiac function during exercise.

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Abbreviations

BMI:

Body mass index

BP:

Blood pressure

CRP:

C-reactive protein

CPET:

Cardiopulmonary exercise testing

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HR:

Heart rate

IFN-γ:

Interferon-gamma

IL-1β:

Interleukin-1-beta

IL-2:

Interleukin-2

IL-4:

Interleukin-4

IL-6:

Interleukin-6

IL-8:

Interleukin-8

IL-10:

Interleukin-10

OSA:

Obstructive sleep apnoea

Q:

Cardiac output

QI:

Cardiac Output Index

SAA:

Serum amyloid A

SV:

Stroke volume

SVI:

Stroke Volume Index

TNF-α:

Tumour necrosis factor-alpha

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Acknowledgements

The authors thank the staff from the David Read Sleep Unit, Respiratory Function Unit, The Children’s Hospital Institute of Sport’s Medicine and Weight Management Service and the Immunology laboratory at The Children’s Hospital at Westmead for contributing and supporting this study. Also, we thank the children and families who agree to participate in this study.

Funding

The National Health and Medical Research Council (NHMRC) provided financial support in the form of a postgraduate scholarship for Dr. Evans. The sponsor had no role in the design or conduct of this research.

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Authors and Affiliations

  1. School of Medicine, University of Sydney, Sydney, NSW, 2006, Australia

    Daniel Hirsch

  2. Department of Medicine, University of Sydney, Sydney, NSW, 2006, Australia

    Carla A. Evans, Rita Machaalani & Karen A. Waters

  3. The Children’s Hospital, Westmead, Sydney, NSW, 2145, Australia

    Melanie Wong, Rita Machaalani & Karen A. Waters

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  1. Daniel Hirsch
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  2. Carla A. Evans
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  3. Melanie Wong
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  4. Rita Machaalani
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  5. Karen A. Waters
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Correspondence to Karen A. Waters.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (name the institution/committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Hirsch, D., Evans, C.A., Wong, M. et al. Biochemical markers of cardiac dysfunction in children with obstructive sleep apnoea (OSA). Sleep Breath 23, 95–101 (2019). https://doi.org/10.1007/s11325-018-1666-y

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  • DOI: https://doi.org/10.1007/s11325-018-1666-y

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