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First sleep apnea drug reduces severity in 70% of trial cases
Sleep apnea can negatively impact health and well-being, but treatment is limited to poorly tolerated positive pressure masks (CPAP) and, in the worst cases, surgery. However, in a recent trial, a nasal spray showed promise as a treatment for the most common sleep-related breathing disorder.
Obstructive sleep apnea (OSA) occurs when the upper airway collapses during sleep, reducing or completely blocking airflow. It’s primarily caused by a combination of impaired throat anatomy and inadequate muscle function during sleep. This leads to a drop in oxygen intake and arousal from sleep, which can have negative health and safety consequences, including daytime tiredness, difficulty focusing, and high blood pressure.
OSA treatment is limited. First-line treatment is a machine that provides continuous positive airway pressure (CPAP) to keep the airway from collapsing. Unfortunately, around half of people who use CPAP machines find them difficult to tolerate. In these cases, surgery to fix the anatomical obstruction may be considered.
Researchers from Flinders University in Australia conducted a small trial using a nasal spray to treat OSA and found it produced promising results.
“Obstructive sleep apnea (OSA) is a sleep disorder where the muscles in the back of the throat relax, and the upper airway narrows or collapses, restricting oxygen intake and causing people to wake repeatedly throughout the night,” said Danny Eckert, a professor at Flinders University’s College and Medicine and Public Health and one of the study’s co-authors. “It has been linked to a variety of medical conditions including cardiovascular disease, stroke, obesity, diabetes, anxiety and depression.”
The researchers tested a nasal spray to deliver a potassium channel blocker topically to the airway muscles to see if it reduced the severity of OSA symptoms.
“Potassium channel blockers are a class of drugs that block the potassium channel in the central nervous system,” said Amal Osman, the lead and corresponding author of the study. “When used in a nasal spray, the blockers have the potential to increase the activity of the muscles that keep the upper airway open and reduce the likelihood of the throat collapsing during sleep.”
Ten people (five women, five men; mean age 55) with OSA randomly received one of three treatments: a placebo nasal spray, a nasal spray containing a potassium channel blocker, or the blocker nasal spray with breathing restricted to ‘nasal only,' which involved the use of mouth tape or a chin strap. On average, participants were obese, had severe OSA, were not overly sleepy and did not have insomnia.
Participants completed three overnight sleep studies with a break of about a week between visits. The researchers found that seven of the 10 study participants showed a modest reduction in OSA severity when the nasal spray was combined with unrestricted breathing versus the placebo. Total oxygen saturation levels were higher with the unrestricted breathing nasal spray treatment than in the placebo group. Morning blood pressure measurements were also lower with the unrestricted breathing spray treatment.
Participants restricted to nose-only breathing did not show improvements despite receiving the potassium channel blocker via nasal spray. Instead, the researchers found that breathing and upper airway muscle function tended to worsen when a chin strap was used.
“What we have discovered is that the nasal spray application of the potassium channel blocker that we tested is safe, well tolerated,” Osman said. “Those who had a physiological improvement in their airway function during sleep also had between 25–45% reductions in markers of their OSA severity, including improved oxygen levels as well as a reduction in their blood pressure the next day.”
The study’s findings offer a new way of expanding treatment options for people with OSA.
“These insights provide a potential pathway for [the] development of new therapeutic solutions for those people with OSA who are unable to tolerate CPAP machines and/or upper airway surgery, and those with a desire for alternatives to existing therapies,” said Eckert. “Right now, there are no approved drugs for treating OSA, but through these findings and future research, we are getting closer to developing new and effective drugs that are safe and easy to use.”
The researchers plan to conduct larger studies to explore their initial findings further.
注释：
apnea: n
表示"呼吸暂停；窒息"，means "transient cessation of respiration"，如：Obesity is a major risk factor for sleep apnea. 肥胖是呼吸暂停的主要危险因素。
Obstructive: n
表示"障碍; 阻碍的；"，means "preventing movement"，如：We'd have made a decision by now if Jean hadn't been so obstructive. 如果不是简如此妨碍，到现在我们早已作出了决定。
表示""，means ""，如：
anatomy: n
表示" 解剖; 解剖学"，means "alternative names for the body of a human being"，如：Various parts of his anatomy were clearly visible. 他身体的各个部分都看得很清楚。
arousal: n
表示"唤醒；激发"，means "the act of arousing"，如：On the negative side, the concepts of activation and arousal are rather amorphous. 从消极方面说，引发和激发这两个概念是很难以捉摸的。
potassium: n
表示" 钾"，如：What fruit vegetable contains potassium most? 什么水果蔬菜含钾最多？
chin strap: n
表示"帽子的颚带"，means "a strap attached to a hat;"，如：This Kapitan also wears a field-green M40 steel helmet with leather chin strap and red Communist star stenciled on the front. 这大尉也戴战地-绿M40钢盔，皮革下巴带，共产主义者红星印在前面。
中文简要说明：
很多人都有浅眠、多梦的睡眠问题，而且通常伴随着巨大的鼾声，不止自己睡不好，连枕边人也遭波及。这类患者都有程度不一的「睡眠呼吸中止症」。目前比较主流的治疗方案是正气压面罩 (CPAP)，但很多人不习惯睡觉还要戴呼吸器。所幸，在最近的试验中，一种新配方的鼻喷剂，有望治疗这种最常见的睡眠障碍。
新阿特拉斯(NewAltas)报导，在睡眠期间，当上呼吸道塌陷、减少或完全阻塞气流时，就会发生阻塞性睡眠呼吸中止症 (OSA)。它主要是肌肉功能不足引起的，当呼吸不顺时，就会导致鼾声，也会导致氧气摄入量下降和浅眠、易醒，对健康和安全产生负面影响，包括白天疲劳、注意力不集中，还有其他心血管疾病、中风、肥胖、糖尿病、焦虑和忧郁。
现在的主要治疗是持续性正压呼吸器 (CPAP)，利用较大的气压，吹起呼吸道。但是一半以上的患者表示他们难以适应，虽然手术也是一种方法，但是临床的经验显示，手术后的肌肉再次塌陷也很常见。
现在，澳洲弗林德斯大学(Flinders University)的研究人员，采用药物治疗方案，以鼻喷剂的形式，将药物作用在上呼吸道肌肉，产生了有希望的结果。
研究主持人艾克特教授(Danny Eckert)说：「我们使用一种钾通道阻断剂，看看它是否可以减轻 OSA 的症状。」
「钾离子通道与神经传导有关，当中枢神经放松时，会放出『休息』的讯号，肌肉也就松弛下来了。但是它发生在上呼吸道肌肉就不是好事，过于放松就导致呼吸中止症。」
该研究的主要作者，奥斯曼教授（Amal Osman）说：「当用于鼻喷剂时，阻断剂有可能增加保持上呼吸道的肌肉活动，也就能减少睡眠期间，软颚到喉咙肌肉塌陷的可能性。」
在自愿者实验中， 10名呼吸中止症患者（5 名女性、5名男性，平均年龄55岁），随机接受三种治疗方法中的一种：安慰型鼻喷剂、含有钾通道阻断剂的鼻喷剂，或仅限「鼻腔」呼吸的阻断剂。
参与者完成了三项夜间睡眠研究，两次实验之间有大约一周的休息时间。研究人员发现，与安慰剂相比，使用阻断剂鼻喷剂的10 名参与者，其中7 名的呼吸中止症略有减轻。不过，效果只作用在「鼻腔」的治疗，明显效果不好，显然它必作用在整个上呼吸道，从鼻腔到咽喉都要作用。
「我们发现，我们测试的钾通道阻断型鼻喷剂，效果是安全的，即使最严重的呼吸中止症，严重程度也降低了 25-45%，血氧值、血压值都有改善。」
当然，目前的实验规模还很小，但通过这些发现和未来的研究，研究人员相信，距离开发安全且易于使用的新型有效药物，目标已越来越近。
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