Acetazolamide Plus Atomoxetine for Obesity Hypoventilation Syndrome Treatment.

These features characterize obesity-hypoventilation syndrome (OHS).

这些特征描述了肥胖低通气综合征（OHS）。

If left untreated, OHS is associated with significant morbidity and mortality.

如果不进行治疗，肥胖低通气综合征（OHS）与显著的发病率和死亡率相关。

Besides lifestyle modifications, positive airway pressure (PAP) is the only available treatment, and it is often not well tolerated.

除了生活方式的改变外，持续气道正压（PAP）是唯一可用的治疗方法，但通常患者耐受性不佳。

Drugs designed to activate UA muscles such as atomoxetine and to stimulate breathing such as acetazolamide represent a potential novel strategy for treating OHS.

旨在激活上气道（UA）肌肉的药物，如阿托莫西汀，以及旨在刺激呼吸的药物，如乙酰唑胺，代表了一种治疗肥胖相关性低通气（OHS）的潜在新策略。

research_question

Is 2 weeks of 500 mg acetazolamide plus 100 mg atomoxetine daily effective for OHS severity (reduction in mean nocturnal CO2 as the primary outcome)?

每天500毫克乙酰唑胺加100毫克阿托莫西汀连续2周，对治疗肥胖相关性低通气（OHS）的严重程度（以夜间平均二氧化碳降低为主要结果）有效吗？

study_design_and_methods

In a randomized, double-masked crossover trial, we compared 2 weeks of acetazolamide plus atomoxetine with placebo in patients with OHS not treated with PAP.

在一项随机、双盲交叉试验中，我们比较了2周的乙酰唑胺加阿托莫西汀与安慰剂在未接受PAP治疗的OHS患者中的效果。

Patients with a BMI of ≥ 35 kg/m2 underwent polysomnography with transcutaneous overnight measurement of CO2 (Ptcco2) and morning blood test to evaluate sleep-related and diurnal hypercapnia at baseline and after each treatment sequence.

BMI ≥ 35 kg/m2的患者进行了多导睡眠图检查，并在夜间通过经皮测量CO2（Ptcco2）和早晨血液测试，以评估基线和每种治疗序列后的睡眠相关和日间高碳酸血症。

Results

Fifteen patients with a median age of 53 years (interquartile range [IQR], 36-59 years; 8 female patients; median BMI, 44 kg/m2 [IQR, 42-53 kg/m2]; baseline median Ptcco2, 49 mm Hg [IQR, 44-55 mm Hg]; median apnea-hypopnea index (AHI), 64 events/h [IQR, 36-83 events/h], and median nocturnal peripheral capillary oxygen saturation (Spo2), 84% [IQR, 79%-89%]) were randomized.

随机分配了15名患者，中位年龄为53岁（四分位数范围[四分位数范围]，36-59岁；8名女性患者；中位BMI为44 kg/m2 [四分位数范围，42-53 kg/m2]；基线中位Ptcco2为49 mm Hg [四分位数范围，44-55 mm Hg]；中位睡眠呼吸暂停低通气指数（AHI）为64次/小时 [四分位数范围，36-83次/小时]，中位夜间外周毛细血管氧饱和度（Spo2）为84% [四分位数范围，79%-89%]）

Acetazolamide plus atomoxetine decreased nocturnal Ptcco2 by a mean of -5.8 mm Hg (95% CI, -7.8 to -3.7 mm Hg; P < .001) and diurnal CO2 compared with placebo.

乙酰唑胺加阿托莫西汀相比安慰剂，降低了夜间Ptcco2的平均值-5.8 mm Hg（95%置信区间，-7.8至-3.7 mm Hg；P < .001）和日间CO2。

Median AHI decreased by -20.9 events/h (95% CI, -26.7 to -15.1 events/h; P < .001) and mean overnight Spo2 increased by 4.3% (95% CI, 2.8%-5.7%; P < .001).

中位数AHI减少了-20.9次/小时（95%置信区间，-26.7至-15.1次/小时；P<.001），平均夜间Spo2增加了4.3%（95%置信区间，2.8%-5.7%；P<.001）。

No serious adverse events occurred.

没有发生严重的不良事件。

interpretation

Our results show that the administration of acetazolamide plus atomoxetine significantly improved sleep-related hypoventilation, oxygen parameters, and AHI in treatment-naive patients with OHS.

我们的研究结果显示，对于未经治疗的OHS患者，联合使用乙酰唑胺和阿托莫西汀显著改善了与睡眠相关的低通气、氧合参数和AHI。

This proof-of-concept study provides encouraging results for a potential pharmacotherapy for OHS.

这项概念验证研究为OHS的潜在药物治疗提供了令人鼓舞的结果。

clinical_trial_registration

ClinicalTrials.gov; No.: NCT05448443; URL: www.

ClinicalTrials.gov; 编号: NCT05448443; 网址: www.

clinicaltrials

gov.

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