Hoff Erik, Strassberger Christian, Zou Ding, Grote Ludger, Stenlöf Kaj, Hedner Jan
Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Region Västra Götaland, Department of Infectious Diseases, Södra Älvsborgs Hospital, Borås, Sweden.
Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Chest. 2024 Mar;165(3):704-715. doi: 10.1016/j.chest.2023.09.022. Epub 2023 Sep 28.
The carbonic anhydrase inhibitor sulthiame reduces OSA severity, increases overnight oxygenation, and improves sleep quality. Insights into how sulthiame modulates OSA pathophysiologic features (endotypic traits) adds to our understanding of the breathing disorder itself, as well as the effects of carbonic anhydrases in respiratory regulation.
How does sulthiame treatment modify endotypic traits in OSA?
Per-protocol tertiary analysis of a randomized controlled trial with the inclusion criteria as follow: BMI, ≥ 20 to ≤ 35 kg/m; age, 18-75 years; apnea-hypopnea index (AHI) ≥ 15 events/h; Epworth sleepiness scale score, ≥ 6; as well as nonacceptance or nontolerance of positive airway pressure treatment. Patients were randomized to receive placebo (n = 22), sulthiame 200 mg (n = 12), or sulthiame 400 mg (n = 24) during 4 weeks of treatment. Polysomnography was applied twice at baseline and follow-up. Endotypic traits were determined from polysomnography tracings (PUPBeta). Sulthiame plasma concentration was analyzed. Differences from baseline to follow-up (Δs) were analyzed with the analysis of covariance or Kruskal-Wallis H test and Pearson (r) or Spearman correlations (r).
Sulthiame (200-mg and 400-mg groups) consistently reduced loop gain (response to a 1-cycle/min disturbance, LG; mean, -0.16 [95% CI, -0.18 to -0.13]; P < .05) in addition to increased ventilation at lowest decile of ventilatory drive (V; median, +12 [95% CI, 4-20]; P < .05) and median ventilation at eupneic ventilatory drive (V; median, +4 [95% CI, 0-5]; P < .05). ΔLG correlated with ΔAHI percentage (200 mg: r = 0.65; P < .05). V and V correlated with ΔAHI (all sulthiame: r = -0.59 and r = -0.65; P < .05 for all). The reduction of LG was seen already in the lower sulthiame concentration range, whereas changes in V peaked in the higher range.
The effect of sulthiame in OSA may be explained by a reduction of ventilatory instability (LG) as well as upper airway collapsibility (V and V).
European Union Drug Regulating Authorities Clinical Trials Database; No.: EudraCT 2017-004767-13; URL: https://www.clinicaltrialsregister.eu.
碳酸酐酶抑制剂舒噻美可降低阻塞性睡眠呼吸暂停（OSA）的严重程度，增加夜间氧合，并改善睡眠质量。深入了解舒噻美如何调节OSA的病理生理特征（内型特征），有助于我们对这种呼吸障碍本身的理解，以及碳酸酐酶在呼吸调节中的作用。
舒噻美治疗如何改变OSA的内型特征？
对一项随机对照试验进行按方案的三级分析，纳入标准如下：体重指数（BMI）≥20至≤35kg/m²；年龄18 - 75岁；呼吸暂停低通气指数（AHI）≥15次/小时；爱泼沃斯嗜睡量表评分≥6分；以及对气道正压治疗不耐受或不接受。患者被随机分为接受安慰剂（n = 22）、舒噻美200mg（n = 12）或舒噻美400mg（n = 24），治疗为期4周。在基线和随访时进行两次多导睡眠图检查。根据多导睡眠图记录（PUPBeta）确定内型特征。分析舒噻美血浆浓度。采用协方差分析或Kruskal - Wallis H检验以及Pearson（r）或Spearman相关性（r）分析从基线到随访的差异（Δs）。
舒噻美（200mg和400mg组）除了在通气驱动最低十分位数时增加通气量（V；中位数，+12[95%CI，4 - 20]；P <.05）和在平静通气驱动时的中位数通气量（V；中位数，+4[95%CI，0 - 5]；P <.05）外，还持续降低环路增益（对每分钟1次周期干扰的反应，LG；平均值，-0.16[95%CI，-0.18至-0.13]；P <.05）。ΔLG与ΔAHI百分比相关（200mg：r = 0.65；P <.05）。V和V与ΔAHI相关（所有舒噻美组：r = -0.59和r = -0.65；均P <.05）。在较低的舒噻美浓度范围内就已观察到LG的降低，而V的变化在较高浓度范围内达到峰值。
舒噻美对OSA的作用可能是通过降低通气不稳定性（LG）以及上气道可塌陷性（V和V）来解释。
欧盟药品监管当局临床试验数据库；编号：EudraCT 2017 - 004767 - 13；网址：https://www.clinicaltrialsregister.eu
