Obstructive Sleep Apnea Is a Distinct Physiological Endotype in Individuals with Comorbid Insomnia and Sleep Apnea (COMISA).

Abstract

With up to 40% of individuals with either insomnia or obstructive sleep apnea (OSA) demonstrating clinically significant symptoms of the other disorder, the high degree of comorbidity amongst the two most common sleep disorders suggests a bi-directional relationship and/or shared underpinnings. Whilst the presence of insomnia disorder is believed to influence the underlying pathophysiology of OSA, this influence is yet to be examined directly. To investigate whether the four OSA endotypes (upper airway collapsibility, muscle compensation, loop gain, and the arousal threshold) are different in OSA patients with and without comorbid insomnia disorder. Using the ventilatory flow pattern captured from routine polysomnography, the four OSA endotypes were measured in 34 OSA patients who met diagnostic criteria for insomnia disorder (COMISA) and 34 OSA patients without insomnia (OSA-only). Patients demonstrated mild-to-severe OSA (AHI: 25.8±2.0 events/h) and were individually matched according to age (50.2±1.5 years) sex (42M:26F), and body mass index (29.3±0.6 kg/m2). Compared to OSA patients without comorbid insomnia, COMISA patients demonstrated significantly lower respiratory arousal thresholds (128.9 [118.1-137.1] vs. 147.7 [132.3-165.0] %Veupnea, U=261, 95%CI[-38.3, -13.9], d=1.1, p<.001), less collapsible upper airways (i.e., higher Vpassive: 88.2 [85.5-94.6] vs. 72.9 [64.7-79.2] %Veupnea, U=1081, 95%CI[14.0, 26.7], d=2.3, p<.001) and more stable ventilatory control (i.e., lower loop gain: 0.51 [0.44-0.56] vs. 0.58 [0.49-0.70], U=402, 95%CI[-0.2, -0.01], d=.05, p=.03). Muscle compensation was similar between groups. Moderated linear regression revealed the arousal threshold moderated the relationship between collapsibility and OSA severity in COMISA, but not OSA-only patients. A low arousal threshold is an overrepresented endotypic trait in individuals with COMISA and may exhibit a greater relative contribution to OSA pathogenesis in these patients. Contrastingly, the prevalence of a highly collapsible upper airway in COMISA was low, suggesting that anatomical predisposition may contribute less to OSA development in COMISA. Based on our findings we theorise that conditioned hyperarousal perpetuating insomnia may translate to a reduced arousal threshold to respiratory events, thereby increasing the risk or severity of OSA. Therapies which target increased nocturnal hyperarousal (e.g., through CBT-I) may be effective in individuals with COMISA.