# Night- to-Night Variability in Sleep Disordered Breathing: Sex and Gender-Related Predictors and Impact on Obstructive Sleep Apnea Clinical Heterogeneity

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $433,403

## Abstract

PROJECT SUMMARY/ABSTRACT
The current standard measure of OSA, the apnea-hypopnea index (AHI) underestimates women’s OSA
severity compared to men, which may lead to missed diagnoses, thus increasing women’s risk for
cardiovascular disease, metabolic and mood disorders, and poor daytime functioning. Most of the early
evidence to support the use of AHI as a measure of OSA severity has been validated in men. There is a
pressing need to identify a reliable biomarker of OSA severity in order to minimize sex and gender inequities in
in diagnosis and management of OSA. We propose to assess night-to-night variability in novel OSA severity
metrics and assess their impact on day-to-day sleepiness, fatigue, mood, and stress towards characterization
of reliable biomarkers of disease severity. The proposed study will leverage cutting-edge sleep monitoring
technology (Cerebra Sleep System) supporting the data collection in the participant’s home over 7 nights. The
study will also collect daytime functioning information several times per day via ecological momentary
assessments (EMA). We will enroll participants from two Sleep Medicine Centers associated with the
University of Pittsburgh and the University of Kansas Medical Center which will allow for a robust recruitment of
300 participants, 100 men, and 200 women balanced by menopausal status. Using available multiple night
recordings, we will assess the within- and between-subject variability of key sleep-disordered breathing
physiological traits (total and sleep stage-specific AHI, hypoxic burden, and pulse rate responses to respiratory
events and to arousals) and determine the role of sex as a potential contributor of between-subject variability in
these traits (Aim 1). Next, we will assess the temporal relationship between novel OSA severity parameters,
sleep traits and daytime function using key objective (sleep duration, architecture, depth, microstructure) and
self-reported sleep traits, as well as EMA of daytime sleepiness, fatigue, mood, and stress (Aim 2). We will
assess the temporal effects of OSA severity parameters on daytime function, determine whether these effects
are mediated by objective sleep traits, and establish whether sex and gender moderate these associations.
Our central hypothesis is that men and women require distinct definitions of OSA severity, because the
mechanisms explaining how sleep disordered breathing impact daytime functioning will be different between
sexes. This study has the potential to create a new paradigm in OSA research that will lead to novel
approaches to OSA severity definitions and improve long term health outcomes for women and men.

## Key facts

- **NIH application ID:** 10991215
- **Project number:** 1R01HL170675-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Diego Mazzotti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $433,403
- **Award type:** 1
- **Project period:** 2024-09-19 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10991215

## Citation

> US National Institutes of Health, RePORTER application 10991215, Night- to-Night Variability in Sleep Disordered Breathing: Sex and Gender-Related Predictors and Impact on Obstructive Sleep Apnea Clinical Heterogeneity (1R01HL170675-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10991215. Licensed CC0.

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