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Communications to the Editor |

Plasma Orexin-A Levels in Obstructive Sleep Apnea-Hypopnea SyndromePlasma Orexin-A Levels in Obstructive Sleep Apnea-Hypopnea Syndrome FREE TO VIEW

Shigeru Sakurai, MD, PhD; Tsuguo Nishijima, MD, PhD; Zenei Arihara, MD, PhD; Kazuhiro Takahashi, MD, PhD
Author and Funding Information

Affiliations: Iwate Medical University School of Medicine, Morioka, Japan,  Tohoku University School of Medicine, Sendai, Japan,  Chiba University, Chiba, Japan

Correspondence to: Shigeru Sakurai, MD, PhD, Third Department of Internal Medicine, Iwate Medical University, 19-1 Ichimaru, Morioka, Japan 020-8505



Chest. 2004;125(5):1963-1964. doi:10.1378/chest.125.5.1963
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To the Editor:

The article by Igarashi et al (October 2003)1reports elevated plasma levels of orexin-A in patients with obstructive sleep apnea-hypopnea syndrome. We have been very surprised at their results, because we have recently reported decreased plasma levels of orexin-A in patients with the same syndrome,2 which is entirely contrary to the findings by Igarashi et al.1Plasma orexin-A levels were correlated negatively with the apnea-hypopnea index, the arousal index, and Epworth sleepiness scale in our study,2 whereas the levels were correlated positively with the apnea-hypopnea index and the arousal index in the study by Igarashi et al.1

One possible reason for this discrepant results may be the difference of the methods. Plasma orexin-A concentrations are very low, and therefore the extraction procedure using Sep-Pak C18 cartridges (Waters Associates; Milford, MA) is essential for the measurement of plasma orexin-A concentrations in our studies.23 However, Igarashi et al1appear to have measured plasma orexin-A levels using a Peninsula radioimmunoassay kit (Peninsula Laboratories; San Carlos, CA) without extraction. In our preliminary study, plasma levels of orexin-A obtained by using a Peninsula radioimmunoassay kit without extraction were nearly 10-fold higher than those obtained by the method Arihara et al.23 There is a good correlation, however, between the levels obtained by these two different methods (r = 0.854, p = 0.011, n = 7) [unpublished observations]. The difference of the methods is therefore unlikely to explain the discrepant results.

Another possible reason for the discrepant results may be the difference of the studied populations. We observed that plasma levels of orexin-A were elevated in cases of mild sleep apnea-hypopnea syndrome, although the levels were decreased in parallel with the severity of the syndrome.2 The baseline characteristics of the subjects are similar, however, between these two studies.12 We excluded patients with renal failure from the study, because plasma orexin-A levels were reported to be elevated in patients with chronic renal failure.4 It is not clear whether patients with renal failure were excluded or not from the study by Igarashi et al.1 Although there was no correlation between plasma orexin-A levels and body mass index in both the studies,12 the presence of obesity may affect plasma orexin-A levels in certain obese cases with sleep apnea-hypopnea syndrome. It was reported that plasma orexin-A levels were decreased with obese subjects.5

Reasons for the discrepant results between Igarashi et al1and ours2 remain to be determined, however. Studies on plasma orexin-A levels in larger populations, and animal studies, if animal models of sleep apnea-hypopnea syndrome are available, would help to clarify the fact on orexin-A in patients with sleep apnea-hypopnea syndrome.

Igarashi, N, Tatsumi, K, Nakamura, A, et al (2003) Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome.Chest124,1381-1385. [CrossRef] [PubMed]
 
Nishijima, T, Sakurai, S, Arihara, Z, et al Plasma orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome.Peptides2003;24,407-411. [CrossRef] [PubMed]
 
Arihara, Z, Takahashi, K, Murakami, O, et al Immunoreactive orexin-A in human plasma.Peptides2001;22,139-142. [CrossRef] [PubMed]
 
Sugimoto, T, Nagake, Y, Sugimoto, S, et al Plasma orexin concentrations in patients on hemodialysis.Nephron2002;90,379-383. [CrossRef] [PubMed]
 
Adam, JA, Menheere, PP, van Dielen, FM, et al Decreased plasma orexin-A levels in obese individuals.Int J Obes Relat Metab Disord2002;26,274-276. [CrossRef] [PubMed]
 

Plasma Orexin-A Levels in Obstructive Sleep Apnea-Hypopnea Syndrome

To the Editor:

We would like to thank Dr. Sakurai et al for their comments. Sakurai et al pointed out the issues regarding the meaning of the levels of plasma/serum substances, including cytokines/hormones, orexin-A in this case. Although the simplicity of specimen collection supports the usefulness of plasma/serum orexin-A as a biological marker of obstructive sleep apnea-hypopnea syndrome (OSAHS), and blood orexin-A levels may represent any aspect of the disease, no researchers have confirmed the exact pathophysiologic meaning of blood levels of orexin-A.

Our findings indicated that plasma orexin-A levels correlated positively with apnea-hypopnea index and arousal index. Considering previous reports,13 which suggested that the plasma levels of orexin-A may represent changes in the number or activity of orexin neurons in the CNS, and the fact that the effects of orexin have been universally recognized to be excitatory,46 our results may not have conflicted with the role of orexin in the CNS. The orexin system may have a neuromodulatory effect on the arousal state. Increased orexin transmission, reflected as increased plasma orexin-A levels, may affect the arousal response in patients with OSAHS.

Whether the extraction procedure using SepPak C18 cartridges is essential to measure plasma orexin-A concentrations cannot be defined, unless the tight linkage between blood orexin-A levels and pathophysiologic state is clarified. Patients with chronic renal failure are known to have elevated levels of plasma orexin-A, but none of the patients had chronic renal failure in our study. Therefore, to elucidate the meaning of blood orexin-A levels, further researches are required to clarify their pathophysiologic meaning.

References
Nishino, S, Repley, B, Overeem, S, et al Hypocretin (orexin) deficiency in human narcolepsy.Lancet2000;355,39-40. [CrossRef] [PubMed]
 
Higuchi, S, Usui, A, Murasaki, M, et al Plasma orexin-A is lower in patients with narcolepsy.Neurosci Lett2002;318,61-64. [CrossRef] [PubMed]
 
Thannickal, TC, Moore, RY, Nienhuis, R, et al Reduced number of hypocretin neurons in human narcolepsy.Neuron2000;27,469-474. [CrossRef] [PubMed]
 
Peyron, C, Tighe, DK, van den Pol, AN, et al Neurons containing hypocretin (orexin) project to multiple neuronal systems.J Neurosci1998;18,9996-10015. [PubMed]
 
Samson, WK, Gosnell, B, Chang, JK, et al Cardiovascular regulatory actions of the hypocretins in brain.Brain Res1999;831,248-253. [CrossRef] [PubMed]
 
Shirasaka, T, Nakazato, M, Takasaki, M, et al Sympathetic and cardiovascular actions of orexins in conscious rats.Am J Physiol1999;46,R1780-R1785
 

Figures

Tables

References

Igarashi, N, Tatsumi, K, Nakamura, A, et al (2003) Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome.Chest124,1381-1385. [CrossRef] [PubMed]
 
Nishijima, T, Sakurai, S, Arihara, Z, et al Plasma orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome.Peptides2003;24,407-411. [CrossRef] [PubMed]
 
Arihara, Z, Takahashi, K, Murakami, O, et al Immunoreactive orexin-A in human plasma.Peptides2001;22,139-142. [CrossRef] [PubMed]
 
Sugimoto, T, Nagake, Y, Sugimoto, S, et al Plasma orexin concentrations in patients on hemodialysis.Nephron2002;90,379-383. [CrossRef] [PubMed]
 
Adam, JA, Menheere, PP, van Dielen, FM, et al Decreased plasma orexin-A levels in obese individuals.Int J Obes Relat Metab Disord2002;26,274-276. [CrossRef] [PubMed]
 
Nishino, S, Repley, B, Overeem, S, et al Hypocretin (orexin) deficiency in human narcolepsy.Lancet2000;355,39-40. [CrossRef] [PubMed]
 
Higuchi, S, Usui, A, Murasaki, M, et al Plasma orexin-A is lower in patients with narcolepsy.Neurosci Lett2002;318,61-64. [CrossRef] [PubMed]
 
Thannickal, TC, Moore, RY, Nienhuis, R, et al Reduced number of hypocretin neurons in human narcolepsy.Neuron2000;27,469-474. [CrossRef] [PubMed]
 
Peyron, C, Tighe, DK, van den Pol, AN, et al Neurons containing hypocretin (orexin) project to multiple neuronal systems.J Neurosci1998;18,9996-10015. [PubMed]
 
Samson, WK, Gosnell, B, Chang, JK, et al Cardiovascular regulatory actions of the hypocretins in brain.Brain Res1999;831,248-253. [CrossRef] [PubMed]
 
Shirasaka, T, Nakazato, M, Takasaki, M, et al Sympathetic and cardiovascular actions of orexins in conscious rats.Am J Physiol1999;46,R1780-R1785
 
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