Apnoea-hypopnoea index of 5 events·h-1 as a metabolomic threshold in patients with sleep complaints

Ott Kiens; Egon Taalberg; Viktoria Ivanova; Ketlin Veeväli; Triin Laurits; Ragne Tamm; Aigar Ottas; Kalle Kilk; Ursel Soomets; Alan Altraja

doi:10.1183/23120541.00325-2022

Apnoea-hypopnoea index of 5 events·h^-1 as a metabolomic threshold in patients with sleep complaints

ERJ Open Res. 2023 Jan 9;9(1):00325-2022. doi: 10.1183/23120541.00325-2022. eCollection 2023 Jan.

Authors

Ott Kiens^{1

2}, Egon Taalberg^{3

4}, Viktoria Ivanova², Ketlin Veeväli⁵, Triin Laurits⁵, Ragne Tamm⁵, Aigar Ottas^{3

4}, Kalle Kilk^{3

4}, Ursel Soomets^{3

4}, Alan Altraja^{1

2}

Affiliations

¹ Department of Pulmonary Medicine, University of Tartu, Tartu, Estonia.
² Lung Clinic, Tartu University Hospital, Tartu, Estonia.
³ Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
⁴ Centre of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia.
⁵ Psychiatry Clinic, Tartu University Hospital, Tartu, Estonia.

Abstract

Background: The apnoea-hypopnoea index (AHI) forms the basis for severity of obstructive sleep apnoea (OSA), a condition expected to reprogramme metabolic pathways in humans. We aimed to identify the AHI breakpoint from which the majority of significant changes in the systemic metabolome of patients with sleep complaints occur.

Methods: In a prospective observational study on symptomatic individuals, who underwent polysomnography for the diagnosis of OSA, profiles of 187 metabolites including amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines and sphingomyelins were analysed with liquid chromatography mass spectrometry in peripheral blood drawn at three different time points overnight. Comparisons of rank-transformed data using a general linear model for repeated measures after dichotomising the study group at different AHI levels were applied to define the best cut-off based on Cohen's f.

Results: 65 subjects were recruited with a median AHI of 15.6 events·h^-1. The mean Cohen's f over the metabolites was highest (0.161) at an AHI level of 5 events·h^-1 representing the metabolomic threshold. Of the particular between-group differences, eight phosphatidylcholines, nine acylcarnitines and one amino acid (threonine) had significantly lower concentrations in the individuals with an AHI level equal to or above the metabolomic threshold. The metabolomic changes at AHI levels defining moderate and severe OSA were smaller than at an AHI of 5 events·h^-1.

Conclusions: The metabolomic threshold for patients with sleep complaints described in this report for the first time coincides with the AHI threshold required to confirm the diagnosis of OSA.