Endotypic Traits of Hypopnea-Predominant OSA: The Role of Hypopnea Criteria.

Abstract

Hypopnea-predominant OSA (HypoOSA) represents a distinct phenotype compared to apnea-predominant OSA. Nevertheless, hypopnea has been defined using varying criteria, leading to differences in the estimation of AHI. This study investigated the endotypic traits of HypoOSA, as defined by ≥ 4% desaturation (4% OD) and ≥ 3% desaturation or arousal (3% ODA) criteria for hypopnea and how AHI and endotypic traits differ by criteria. We prospectively enrolled 765 adult patients with moderate-to-severe OSA from a single sleep centre. Endotypic traits were obtained from in-laboratory polysomnographic studies. Respiratory events were scored twice using 3% ODA and 4% OD criteria. Endotypic traits characterizing HypoOSA, defined as AHI comprising < 50% apneas, were identified and compared to apnea-predominant OSA. Within-subject differences in endotypic traits between the hypopnea criteria were analysed. We observed that 4% OD and 3% ODA identified 40.3% and 57.0% patients as HypoOSA, respectively. Compared to apnea-predominant OSA, HypoOSA was characterized by a lower arousal threshold, higher compensation and less collapsible upper airway, regardless of hypopnea criteria used. Compared with the 4% OD criterion, the 3% ODA criterion for hypopnea increased AHI by 33%, whereas the proportion of time with SpO₂ < 90% and endotypic traits showed less variation. Patients with low consistency in AHI estimates between the two criteria showed lower AHI and favourable upper airway pathology compared to the high consistency group. In conclusion, HypoOSA is characterized by lower arousal threshold and favourable upper airway patency. Different hypopnea criteria resulted in variation in AHI, particularly among patients with lower AHI, whereas hypoxic burden and endotypic traits remained relatively stable.