Ventilatory chemoresponsiveness, narcolepsy-cataplexy and human leukocyte antigen DQB1*0602 status.
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)-DQB1*0602 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-DQB1*0602 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.
Han
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Dept of Pulmonary Medicine, The People's Hospital, Beijing University, Beijing 100044, China. hanfang1@hotmail.com
Mignot
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Wei
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Dong
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Li
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Lin
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An
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Wang
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Wang
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He
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Gao
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Li
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Gao
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Strohl
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D000328:Adult; D015992:Body Mass Index; D002385:Cataplexy / Q000235:genetics / Q000276:immunology*; D002681:China; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics / Q000502:physiology*; D059866:HLA-DQ beta-Chains; D006801:Humans; D006935:Hypercapnia; D000860:Hypoxia; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D009290:Narcolepsy / Q000235:genetics / Q000276:immunology*; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D012119:Respiration; D012129:Respiratory Function Tests; D012890:Sleep; D012893:Sleep Wake Disorders / Q000378:metabolism
C000596229:HCRT protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D000068797:Orexins