Atomoxetine and fesoterodine combination improves obstructive sleep apnoea severity in patients with milder upper airway collapsibility.
Atomoxetine and fesoterodine combination improves obstructive sleep apnoea severity in patients with milder upper airway collapsibility.
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DOI：
10.1111/resp.14326
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发表时间：
2022-11
期刊：
影响因子：
6.9
通讯作者：
Sands, Scott A.
中科院分区：
文献类型：
--
作者：
Messineo, Ludovico;Taranto-Montemurro, Luigi;Calianese, Nicole;Gell, Laura K.;Azarbarzin, Ali;Labarca, Gonzalo;Vena, Dan;Yang, Hyung Chae;Wang, Tsai-Yu;Wellman, Andrew;Sands, Scott A.
去甲肾上腺素能托莫西汀与抗毒蕈碱奥昔布宁联合治疗可显著增加颏舌肌活动，降低阻塞性睡眠呼吸暂停（OSA）的严重程度。然而，奥昔布宁的半衰期比托莫西汀短，副作用可能会阻碍长期使用。因此，我们的目的是测试托莫西汀和非索罗定（Ato-Feso）（一种新型抗毒蕈碱缓释制剂）联合治疗对OSA严重程度和内型的影响。12例OSA受试者接受了一项随机、双盲、交叉试验，比较了一晚托莫西汀+非索罗定（80-4 mg）与安慰剂。OSA严重程度的参数（例如呼吸暂停低通气指数[AHI]、最低氧饱和度下降、缺氧负荷）由两项临床、实验室多导睡眠图研究计算。OSA内型（包括每个VMIN的可扩展性和唤醒阈值）来自经验证的算法。与安慰剂相比，Ato-Feso没有降低AHI（34.2±19.1 vs. 30.1±28.2事件/小时，P=0.493），但降低了呼吸暂停指数（12.9[28.8] vs. 1.8[9.1]起事件/小时，中位数[IQR]，P=0.027），最低饱和度下降增加[76.8[8.0] vs. 82.2[8.8] %，P=0.003）;观察到低氧负荷改善的非显著趋势（52.4[50.5] % min/hr对29.7[78.9] %min/hr，P=0.093）。Ato-Feso降低了活动性（VMIN升高（43.7[29.8 <$55.7] vs. 56.8[43.8 <$69.8] %VEUPNEA，平均值[CI]，P=0.002），但降低了唤醒阈值（129.3[120.1 <$138.6] vs. 116.7[107.5 <$126] %VEUPNEA，P=0.038）。在事后分析中，N=6/6例具有较轻可耐受性（VMIN>43%）的患者表现出OSA消退（AHI下降>50%且残余AHI<10次事件/h）和改善的低氧血症。虽然在COPD患者中无效，但Ato-Feso给药一晚可抑制轻度COPD患者的OSA。Ato-Feso可能在某些亚组的个体中作为替代OSA治疗有一定的希望。
The combination of the noradrenergic atomoxetine plus the anti-muscarinic oxybutynin acutely increased genioglossus activity and reduced obstructive sleep apnea (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. 12 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. apnea-hypopnea index [AHI], nadir oxygen desaturation, hypoxic burden) were calculated from two clinical, in-lab polysomnographic studies. OSA endotypes (including collapsibility per VMIN 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/hr, P=0.493), but reduced the apnea index (12.9[28.8] vs. 1.8[9.1] events/hr, median[IQR], P=0.027), 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/hr, P=0.093). Ato-Feso lowered collapsibility (raised VMIN (43.7[29.8‒55.7] vs. 56.8[43.8‒69.8] %VEUPNEA, mean[CI], P=0.002), but reduced the arousal threshold (129.3[120.1‒138.6] vs. 116.7[107.5‒126] %VEUPNEA, P=0.038). In post-hoc analysis, N=6/6 patients with milder collapsibility (VMIN>43%) exhibited OSA resolution (drop in AHI>50% and residual AHI<10 events/h) and improved hypoxemia. 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.
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影响因子：
9.6
作者：
Perger, Elisa;Montemurro, Luigi Taranto;Rosa, Debora;Vicini, Stefano;Marconi, Mariapaola;Zanotti, Lucia;Meriggi, Paolo;Azarbarzin, Ali;Sands, Scott A.;Wellman, Andrew;Lombardi, Carolina;Parati, Gianfranco
通讯作者：
Parati, Gianfranco
DOI：
10.1183/09031936.00062914
发表时间：
2015-02
期刊：
The European respiratory journal
影响因子：
--
作者：
Terrill PI;Edwards BA;Nemati S;Butler JP;Owens RL;Eckert DJ;White DP;Malhotra A;Wellman A;Sands SA
通讯作者：
Sands SA
DOI：
10.1164/rccm.201209-1654oc
发表时间：
2013-02-01
影响因子：
24.7
作者：
Grace, Kevin P.;Hughes, Stuart W.;Horner, Richard L.
通讯作者：
Horner, Richard L.
影响因子：
5.6
作者：
Sands, Scott A.;Terrill, Philip I.;Wellman, Andrew
通讯作者：
Wellman, Andrew
影响因子：
5.5
作者：
Messineo, Ludovico;Eckert, Danny J.;Carberry, Jayne C.
通讯作者：
Carberry, Jayne C.