Dept of Pulmonary Medicine, The People's Hospital, Beijing University, Beijing 100044, China.
Eur Respir J. 2010 Sep;36(3):577-83. doi: 10.1183/09031936.00174609. Epub 2010 Jan 28.
We hypothesised that hypocretin (orexin) plays a role in the determination of ventilatory chemosensitivity. 130 patients with narcolepsy-cataplexy (mean ± SD age 20 ± 10 yrs, 69% male) and 117 controls (22 ± 6.9 yrs, 62% male) were recruited and tested for human leukocyte antigen (HLA)-DQB10602 status, hyperoxia hypercapnic (change in minute ventilation (δV'(E))/carbon dioxide tension (δP(CO(2))) L·min(-1)·mmHg(-1)) and hypoxic (δV'(E) /change in arterial oxygen saturation measured by probe oximetry (δS(p,O(2))) L·min(-1) per %S(p,O(2))) responsiveness, and by spirometry. Hypocretin deficiency was determined either by measures of cerebrospinal fluid hypocretin-1 (37 patients) or by positive HLA-DQB10602 status. All patients and 49% of controls underwent polysomnography and multiple sleep latency testing. Despite similar spirometric values, patients had a higher apnoea/hypopnoea index (AHI) (2.8 ± 5.4 versus 0.8 ± 1.6 h(-1); p = 0.03) and lower minimal oxygen saturation during sleep (87% ± 7 versus 91 ± 4%; p = 0.0002), independent of age, sex and body mass index. Patients had depressed hypoxic responsiveness (0.13 ± 0.09 versus 0.19 ± 0.13 L·min(-1) per %S(p,O(2)); p<0.0001), independent of AHI, but hypercapnic responsiveness did not differ. Examined by HLA status, positive (26 out of 117) controls had lower hypoxic but similar hypercapnic responsiveness than those marker-negative (0.13 ± 0.08 versus 0.20 ± 0.14 L·min(-1) per %S(p,O(2)); p<0.0001). Thus, a lower hypoxic responsiveness in the narcolepsy-cataplexy group is a result of DQB1*0602 status rather than the clinical features of disease.
我们假设下丘脑分泌素（orexin）在确定通气化学敏感性方面发挥作用。 130 名发作性睡病伴猝倒症患者（平均年龄±标准差 20 ± 10 岁，69%为男性）和 117 名对照者（22 ± 6.9 岁，62%为男性）被招募并检测人类白细胞抗原（HLA）-DQB10602 状态、高氧高碳酸血症（分钟通气量（δV'（E））/二氧化碳分压（δP（CO（2）））的变化（L·min（-1）·mmHg（-1））和低氧（δV'（E）/脉搏血氧饱和度测定探头（δS（p，O（2））的变化（L·min（-1）/%S（p，O（2））））和肺活量测定。 下丘脑分泌素缺乏症通过脑脊液下丘脑分泌素-1 测量（37 例）或 HLA-DQB10602 阳性状态确定。 所有患者和 49%的对照者进行多导睡眠图和多次睡眠潜伏期测试。 尽管肺活量测定值相似，但患者的呼吸暂停/低通气指数（AHI）更高（2.8 ± 5.4 比 0.8 ± 1.6 h（-1）；p = 0.03），睡眠时最低氧饱和度更低（87% ± 7 比 91 ± 4%；p = 0.0002），与年龄、性别和体重指数无关。 患者的低氧反应性降低（0.13 ± 0.09 比 0.19 ± 0.13 L·min（-1）/%S（p，O（2））；p<0.0001），与 AHI 无关，但高碳酸血症反应性无差异。 根据 HLA 状态检查，26 名阳性（117 名中的 26 名）对照者的低氧反应性低于标记阴性者（0.13 ± 0.08 比 0.20 ± 0.14 L·min（-1）/%S（p，O（2））；p<0.0001）。 因此，发作性睡病-猝倒症组的低氧反应性是 DQB1*0602 状态的结果，而不是疾病的临床特征。
