Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, Massachusetts, USA.
Department of Allergy Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, Victoria, Australia.
Respirology. 2022 Nov;27(11):975-982. doi: 10.1111/resp.14326. Epub 2022 Jul 10.
The combination of the noradrenergic atomoxetine plus the anti-muscarinic oxybutynin acutely increased genioglossus activity and reduced obstructive sleep apnoea (OSA) severity. However, oxybutynin has shorter half-life than atomoxetine and side effects that might discourage long-term usage. Accordingly, we aimed to test the combination of atomoxetine and fesoterodine (Ato-Feso), a newer anti-muscarinic with extended release formulation, on OSA severity and endotypes.
Twelve subjects with OSA underwent a randomized, double-blind, crossover trial comparing one night of atomoxetine plus fesoterodine (80-4 mg) to placebo. Parameters of OSA severity (e.g., apnoea-hypopnoea index [AHI], nadir oxygen desaturation and hypoxic burden) were calculated from two clinical, in-lab polysomnographic studies. OSA endotypes (including collapsibility per V and arousal threshold) were derived from validated algorithms.
Compared to placebo, Ato-Feso did not reduce the AHI (34.2 ± 19.1 vs. 30.1 ± 28.2 events/h, p = 0.493), but reduced the apnoea index (12.9 [28.8] vs. 1.8 [9.1] events/h, median [interquartile range], p = 0.027) and increased nadir desaturation (76.8 [8.0] vs. 82.2 [8.8] %, p = 0.003); a non-significant trend for improved hypoxic burden was observed (52.4 [50.5] vs. 29.7 [78.9] %min/h, p = 0.093). Ato-Feso lowered collapsibility (raised V ; 43.7 [29.8-55.7] vs. 56.8 [43.8-69.8] %V , mean [CI], p = 0.002), but reduced the arousal threshold (129.3 [120.1-138.6] vs. 116.7 [107.5-126] %V , p = 0.038). In post hoc analysis, 6/6 patients with milder collapsibility (V > 43%) exhibited OSA resolution (drop in AHI > 50% and residual AHI < 10 events/h) and improved hypoxaemia.
While inefficacious in unselected patients, Ato-Feso administered for one night suppressed OSA in patients with milder collapsibility. Ato-Feso may hold some promise as an alternative OSA treatment in certain subgroups of individuals.
去甲肾上腺素能药物托莫西汀联合抗毒蕈碱药物奥昔布宁可急性增加颏舌肌活性，降低阻塞性睡眠呼吸暂停（OSA）严重程度。然而，奥昔布宁的半衰期短于托莫西汀，且具有可能会阻碍长期使用的副作用。因此，我们旨在研究托莫西汀与新型延长释放抗毒蕈碱药物非索罗定（Ato-Feso）联合用药对 OSA 严重程度和表型的影响。
12 名 OSA 患者接受了一项随机、双盲、交叉临床试验，比较了一晚上服用托莫西汀加非索罗定（80-4mg）与安慰剂的效果。OSA 严重程度的参数（如呼吸暂停低通气指数[AHI]、最低氧饱和度下降和低氧负荷）是根据两项临床、实验室多导睡眠图研究计算得出的。OSA 表型（包括 V 塌陷率和觉醒阈值）是通过验证算法得出的。
与安慰剂相比，Ato-Feso 并未降低 AHI（34.2±19.1 比 30.1±28.2 次/小时，p=0.493），但降低了呼吸暂停指数（12.9[28.8]比 1.8[9.1]次/小时，中位数[四分位距]，p=0.027）和最低氧饱和度下降（76.8[8.0]比 82.2[8.8]%，p=0.003）；观察到低氧负荷有改善的趋势（52.4[50.5]比 29.7[78.9]%/小时，p=0.093）。Ato-Feso 降低了 V 塌陷率（升高了 V 值；43.7[29.8-55.7]比 56.8[43.8-69.8]%V，平均值[CI]，p=0.002），但降低了觉醒阈值（129.3[120.1-138.6]比 116.7[107.5-126]%V，p=0.038）。在事后分析中，6/6 例 V 值较轻（V>43%）的患者出现 OSA 缓解（AHI 下降>50%，残余 AHI<10 次/小时）和改善的低氧血症。
虽然在未选择的患者中无效，但 Ato-Feso 在 V 值较轻的患者中可抑制 OSA。Ato-Feso 可能作为特定亚组人群的 OSA 治疗的替代选择有一定的前景。
