Cholinergic Markers and Cytokines in OSA Patients

Reale, Marcella; Velluto, Lucia; Nicola, Marta Di; D’Angelo, Chiara; Costantini, Erica; Marchioni, Michele; Cerroni, Gianluigi; Guarnieri, Biancamaria

doi:10.3390/ijms21093264

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…However, no correlation was found between plasma choline levels and ESS scores. 43 Causes of the discrepancies in these studies remain unclear. Also, we cannot explain the association mechanism between lower plasma ACh levels and self-reported sleepiness.…”

Section: Discussionmentioning

confidence: 99%

Depression of Non-Neuronal Cholinergic System May Play a Role in Co-Occurrence of Subjective Daytime Sleepiness and Hypertension in Patients with Obstructive Sleep Apnea Syndrome

Meng¹,

Sun²,

Chen³

et al. 2021

NSS

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Purpose Simultaneous occurrence of hypertension and excessive daytime sleepiness (EDS) is very common in obstructive sleep apnea syndrome (OSAS), although no study has specifically addressed this issue. The present study explored the risk factors for co-occurrence of OSAS-related EDS and hypertension. Patients and Methods A total of 161 OSAS patients were studied after undergoing an eight-hour in-laboratory polysomnography for one night. The OSAS severity assessment depends on the number of breathing disturbances per hour of sleep. EDS was defined using the Epworth Sleepiness Scale (ESS) scores of ≥13. Hypertension was defined according to direct cuff blood pressure (BP) measurements. Beat-to-beat R-R interval data were incorporated in polysomnography for heart rate variability analysis. The low-frequency/high-frequency band ratio was used to reflect sympathovagal balance. The study participants were divided into four groups based on the presence of EDS and/or hypertension: EDS with hypertension (n = 53), EDS without hypertension (n = 27), no EDS with hypertension (n = 38), and no EDS or hypertension (n = 43). Clinical, polysomnographic and heart rate data were compared and studied among the four groups. Plasma acetylcholine (ACh) levels were assessed to explore the effects of the non-neuronal cholinergic system and the co-occurrence of EDS and hypertension. Results Patients with EDS and hypertension had more severe OSAS severity indices compared to control patients. Increased cardiac sympathovagal imbalance and nocturnal hypoxemia regulated the presence of EDS and hypertension. Further plasma biomarker analysis revealed that both ESS scores and BP levels were associated with significantly elevated plasma norepinephrine, interleukin-6 and superoxide dismutase levels and significantly decreased ACh levels. Logistic regression analyses showed that ACh was the only factor significantly associated with co-occurrence of EDS and hypertension after controlling for confounders using odds ratio of 0.932, with a 95% confidence interval of 0.868 to 1.000 ( P = 0.049). Conclusion The results suggested that OSAS coupled with both EDS and hypertension is a more severe phenotype of the respiratory disorder. The presence of EDS and hypertension was accompanied by sympathovagal imbalance, and co-occurrence of these two conditions may be related to decreased plasma ACh levels.

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Section: Discussionmentioning

confidence: 99%

Depression of Non-Neuronal Cholinergic System May Play a Role in Co-Occurrence of Subjective Daytime Sleepiness and Hypertension in Patients with Obstructive Sleep Apnea Syndrome

Meng¹,

Sun²,

Chen³

et al. 2021

NSS

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“…Therefore, interest focus on exploring biomarkers has been increasing for decades. In recent years, additional research on cellular immune has reported that macrophage polarization towards M1 subsets ( Khalyfa, Kheirandish-Gozal & Gozal, 2018 ), increased ratio of NLR ( Rha et al., 2020 ), PLR ( Kıvanc et al., 2018 ), CD8+T/CD4+T ( Domagała-Kulawik et al., 2015 ), and Th17/Treg ( Reale et al., 2020 ), as well as DNA methylation of toll-like receptor 2/6 ( Huang et al., 2020 ) in OSA patients, suggesting possible reactions to new endogenous antigens. Given the vital role of T cells in adaptive immunity, the question arises as to why and how T cell immunity is impaired in OSA.…”

Section: Discussionmentioning

confidence: 99%

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

Zhuo

et al. 2023

PeerJ

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Background Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. Methods We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. Results We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R = 0.603) and smoking (R = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Conclusions Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.

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“…The possible mechanism includes changes in intrathoracic pressure, meaning that the increase in pleural negative pressure can lead to mechanical stretch of the aorta (54,55,(59)(60)(61), which further leads to the expansion of the aortic root, thoracic aorta and thoracic FL; patients with frequent intermittent hypoxia leading to oxidative stress and increases in sympathetic activity exhibit an increase in blood pressure due to the activation of the renin-angiotensin-aldosterone system (59,60,62). The state of chronic intermittent hypoxemia and the altered microenvironment in OSA patients, such as the increase in IL-6 levels and reduction in TGF-β levels, could damage the function of endothelial cells and promote a Th17/Treg imbalance, which leads to a reduction in the production of endotheliumdependent vasodilator substances and contributes to vascular dysfunction and stimulation of systemic inflammation (63)(64)(65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnoea in Stanford Type B Aortic Dissection Is Associated With Multiple Imaging Signs Related to Late Aortic Events

Zhang

et al. 2021

Front. Cardiovasc. Med.

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Background: Obstructive sleep apnoea (OSA) is highly prevalent in patients with Stanford type B aortic dissection (TBAD). Few studies have evaluated the effects of OSA on vascular changes in TBAD patients. This study aimed to explore the effect of OSA on aortic morphological changes in TBAD patients and its relation to late aortic events (LAEs).Methods: This case-control study included 143 TBAD patients. The diameters of different parts of the aorta were measured based on computed tomography angiography (CTA). According to the apnoea-hypopnoea index (AHI), OSA was classified as mild (5 ≤ AHI ≤ 15), moderate (15 < AHI ≤ 30), or severe (AHI > 30). The false lumen (FL) status was evaluated and classified as partially thrombosed, patent, or completely thrombosed.Results: The OSA prevalence in TBAD patients was 64.3%, and image differences related to LAEs between TBAD patients with and without OSA included the maximum aortic diameter at onset (37.3 ± 3.9 vs. 40.3 ± 4.5 mm, p < 0.001), the FL diameter of the proximal descending thoracic aorta (16.0 ± 6.8 vs. 20.3 ± 4.7 mm, p < 0.001), and the proportion of the FL that was partially thrombosed (39.2 vs. 64.1%, p = 0.004). Additionally, in the multivariable analysis of patients with OSA, the risks of an aortic diameter ≥40 mm, a proximal descending aorta FL ≥ 22 mm and a partially thrombosed FL were 4.611 (95% CI: 1.796–11.838, p = 0.001), 2.544 (95% CI: 1.050–6.165, p = 0.039), and 2.565 (95% CI: 1.167–5.637, p = 0.019), respectively, after adjustment for confounding factors. Trend tests showed that the risks of an aortic diameter ≥40 mm and a partially thrombosed FL increased with increasing OSA severity.Conclusions: TBAD patients with moderate to severe OSA have aortic dilatation in different parts of the aorta. OSA is an independent risk factor for multiple imaging signs related to LAEs, suggesting that OSA is an important factor affecting the prognosis of TBAD patients.

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Cholinergic Markers and Cytokines in OSA Patients

Cited by 12 publications

References 32 publications

Depression of Non-Neuronal Cholinergic System May Play a Role in Co-Occurrence of Subjective Daytime Sleepiness and Hypertension in Patients with Obstructive Sleep Apnea Syndrome

Depression of Non-Neuronal Cholinergic System May Play a Role in Co-Occurrence of Subjective Daytime Sleepiness and Hypertension in Patients with Obstructive Sleep Apnea Syndrome

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

Obstructive Sleep Apnoea in Stanford Type B Aortic Dissection Is Associated With Multiple Imaging Signs Related to Late Aortic Events

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