Study Objectives Obstructive sleep apnea (OSA) exhibits cyclical patterns of respiratory events followed by hyperpneic breaths which frequently coincide with arousals. While this hyperventilation partially results from accumulated respiratory stimuli, arousal (i.e., its presence and intensity) appears to contribute independently. As such, this study aims to quantify the relative contributions of arousal presence and intensity to post-event ventilation independent of chemoreflex-driven responses.

Methods This study utilized two retrospective polysomnography (PSG) data sets, comprising a community-based (Multi-Ethnic Study of Atherosclerosis, MESA, N=1781) and the Physiological Study data set (N=67). Arousal presence (0/1), arousal intensity (range 0-9), and post-event ventilation were calculated for each respiratory obstructive event for all participants using computational models. Mixed-effects linear models were used to examine the association between arousal presence and intensity, and post-event ventilation at both inter-event and inter-participant levels.

Results At the inter-event level, arousal presence at respiratory event termination increased ventilation by 17-30%Eupnea (increase above eupneic baseline) in both data sets, where each step increment in arousal intensity contributed an additional 1-4%Eupnea increase in ventilation. At the inter-participant level, each step increment of overnight mean arousal intensity was associated with 2-4%Eupnea increase in ventilatory response to arousal in both data sets.

Conclusions Our findings demonstrate that arousal presence plays an essential role in elevating post-event hyperventilation in OSA, with arousal intensity exerting modest influence per increment, but substantial cumulative effects at moderate-high levels. These results, consistent across both data sets, suggest a distinct mechanistic pathway to post-event hyperventilation beyond chemoreflex stimulation.

The authors have declared no competing interest.

This study was supported by grants from the National Health and Medical Research Council of Australia (NHMRC Grant No. 2001729 and 2007001), the State Research Funding for university-level health research, Kuopio University Hospital, Wellbeing services county of North Savo (5041820), and the Research Council of Finland (361199).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Mass General Brigham Institutional Review Board gave ethical approval for this work (2019P000666). The Research Ethics and Integrity Board of The University of Queensland gave the ethical approval for this work (HE000630 and HE002256).

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Data availability statement: The MESA data set is publicly available from NSRR repository. The Physiological Study data set used and analyzed in the current study is available from the corresponding author upon reasonable request.

Funding: This study was supported by grants from the National Health and Medical Research Council of Australia (NHMRC Grant No. 2001729 and 2007001), the State Research Funding for university-level health research, Kuopio University Hospital, Wellbeing services county of North Savo (5041820), and the Research Council of Finland (361199).

Conflict of Interest: No conflict of interest to declare

The MESA data set is publicly available from NSRR repository. The Physiological Study data set used and analyzed in the current study is available from the corresponding author upon reasonable request.