Oral breathing and oxygenation stability during wakefulness: Identifying an unresolved question in respiratory physiology.

Arterial oxygen saturation is traditionally interpreted using threshold-based paradigms in which physiological significance is primarily attributed to overt hypoxemia. However, evidence from sleep physiology and integrative respiratory research suggests that oxygenation dynamics, including the cumulative burden of transient oxygen desaturation, may provide complementary physiological information beyond average oxygen saturation alone. Whether similar concepts are relevant during wakefulness remains largely unexplored. Among the factors that could influence oxygenation dynamics, breathing route has received surprisingly little attention. Although nasal breathing has recognized advantages for airflow conditioning, nitric oxide delivery, and upper airway mechanics, direct evidence demonstrating that oral breathing alters oxygenation stability during wakefulness is currently lacking. Existing studies instead provide indirect observations and identify important knowledge gaps rather than establishing causal relationships. Here, we propose a conceptual framework in which breathing route is proposed as an experimental model for investigating oxygenation stability during wakefulness. We discuss physiological mechanisms that could plausibly link breathing route to ventilatory efficiency, ventilation-perfusion matching, chemoreflex activation, autonomic regulation, and mitochondrial redox signaling, while emphasizing that these mechanisms remain hypothetical and require direct experimental validation. Rather than arguing that oral breathing causes clinically relevant oxygen desaturation, this Perspective identifies an unresolved question in respiratory physiology and outlines experimentally testable hypotheses to determine whether oxygenation stability represents a previously overlooked physiological variable during wakefulness.