Increased urinary leukotriene E4 excretion in obstructive sleep apnea: Effects of obesity and hypoxia

Stanke‐Labesque, Françoise; Bäck, Magnus; Lefebvre, Blandine; Tamisier, Renaud; Baguet, Jean-Philippe; Arnol, Nathalie; Lévy, Patrick; Pépin, Jean‐Louis

doi:10.1016/j.jaci.2009.05.033

Cited by 50 publications

(48 citation statements)

References 34 publications

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“…Due to confounders and cardiovascular risk factors in our patients, we cannot exclude that LTB 4 pathway activation by IH may not be the sole mechanism of vascular remodeling. Notably, LTA 4 H expression correlated with BMI but not oxygen desaturation, whereas FLAP expression was infl uenced by oxygen desaturation and obesity as reported ( 5,18 ). Similarly, FLAP mRNA and protein levels were signifi cantly higher in PMNs derived from OSA patients versus controls, which supports the suggested mechanism, but our data demonstrated only trend correlation of FLAP mRNA with percentage of time spent with SaO 2 < 90%.…”

Section: Discussionsupporting

confidence: 71%

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Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea

Stanke‐Labesque

Pépin

Jouvencel

et al. 2012

Journal of Lipid Research

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Obstructive sleep apnea (OSA) patients experience recurring episodes of partial or complete upper airway obstruction during sleep. Upper airway collapse is usually associated with desaturation-reoxygenation, harming the cardiovascular system. Moderate to severe OSA patients show signs of early atherosclerosis ( 1-3 ).Recent studies have associated the infl ammatory mediators, leukotrienes (LTs), with both OSA ( 4-7 ) and atherosclerosis ( 8, 9 ). However, the mechanisms involved in the role of LTs as a link between OSA and atherosclerosis have remained largely unexplored.LTs are synthesized on activation of 5-lipoxygenase (5-LO) ( 10 ), which interacts with nuclear membrane-bound 5-LO-activating protein (FLAP) ( 11 ), generating leukotriene A 4 (LTA 4 ) in infl ammatory cells ( 12 ). In polymorphonuclear neutrophils (PMNs), LTA 4 is converted by LTA 4 hydrolase (LTA 4 H) into LTB 4 , which modulates transcription or is secreted to mediate autocrine or paracrine effects through the BLT 1 and BLT 2 receptors. LTB 4 is a potent chemoattractant, facilitating leukocyte adhesion to endothelial cell and recruitment, critical steps in atherosclerosis. Thus, LTB 4 function in the pathogenesis of atherosclerosis is well established ( 8, 13 ).Abstract Leukotriene B 4 (LTB 4 ) production increases in obstructive sleep apnea syndrome (OSA) and is linked to early vascular remodeling, the mechanism of which is unknown. The objective of this study was to to determine the molecular mechanisms of LTB 4 pathway activation in polymorphonuclear cells (PMNs) and early vascular remodeling in OSA and the specifi c contribution of intermittent hypoxia (IH). PMNs were isolated from 120 OSA patients and 33 healthy subjects and used for measurements of LTB 4 production, determination of mRNA and protein expression levels, or exposed for four cycles of in vitro IH. PMNs derived from OSA patients exhibited increased LTB 4 production, for which apnea-hypopnea index was an independent predictor ( P =0.042). 5-Lipoxygenase-activating protein (FLAP) mRNA and protein increased signifi cantly in PMNs from OSA patients versus controls and were associated with carotid luminal diameter and intima-media thickness. LTB 4 (10 ng/ml) increased IL-6 ( P =0.006) and MCP-1 ( P =0.002) production in OSA patient monocytes. In vitro exposure of PMNs from controls to IH enhanced FLAP mRNA levels ( P = 0.027) and induced a 2.7-fold increase ( P =0.028) in LTB 4 secretion compared with PMNs exposed to normoxia. In conclusion, upregulation of FLAP in PMNs in response to IH may participate in early vascular remodeling in OSA patients, suggesting FLAP as a potential therapeutic target for the cardiovascular morbidity associated with OSA.

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Section: Discussionsupporting

confidence: 71%

“…Nocturnal polysomnography was performed in all subjects as described ( 5 ). Sleep apnea was defi ned as apnea-hypopnea index (AHI) >5 per h of sleep and respiratory disturbance index (RDI) including fl ow limitation episodes >15 and symptoms ( 17 ).…”

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confidence: 99%

Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea

Stanke‐Labesque

Pépin

Jouvencel

et al. 2012

Journal of Lipid Research

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“…overlap syndrome [74]. The role of obesity per se remains highly controversial as in some studies SDB seems to be the only contributing factor of vascular inflammation and dysfunction [75], while obesity has been evidenced as a source of oxidative stress and inflammation [76,77].…”

Section: Osa Intermittent Hypoxia and Cardiovascular And Metabolic Cmentioning

confidence: 99%

“…However, urinary LTE 4 , a validated marker of pro-inflammatory cysteinyl LT production, was mainly related with obesity and, to a lesser extent, hypoxia severity ( fig. 2) [77].…”

Section: Osa Intermittent Hypoxia and Cardiovascular And Metabolic Cmentioning

confidence: 99%

Sleep apnoea syndrome in 2011: current concepts and future directions

Lévy¹,

Tamisier²,

Minville³

et al. 2011

Eur Respir Rev

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“…OSA has been shown to be associated with inflammation of both the upper and lower airways too [4]. While a number of pathophysiological mechanisms may contribute to OSA formation, CysLTs play a major role with not only local effects but also with systemic relations especially in children with adenotonsillar hypertrophy [5][6][7][8]. Besides adenotonsillar hypertrophy, many nose and pharynx abnormalities such as septal deviation, nasal polyps, turbinate hypertrophy, and rhinitis may cause OSA [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Is there any asociation between obstructive sleep apnea (OSA) and aspirin-exacerbated respiratory disease (AERD)? Does aspirin desensitization affect OSA risk?

Tepetam¹,

Afşar²

2017

Dis Disord

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Objective: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, eosinophilic rhinosinusitis, recurrent nasal polyposis, and hypersensitivity reactions to aspirin or any other nonsteroidal antiinflammatory drugs (NSAİDs). In our study, we thought that, in adult patients with AERD, obstructive sleep apnea (OSA) may develop more frequently due to both lower and upper respiratory tract inflammation associated with cysLTs; and so we compared OSA frequency and severity in patients with AERD, asthma with rhinosinusitis without hypersensitivity reaction to aspirin or NSAIDs ( Aspirin tolerant respiratory disease; ATRD) and in patients without asthma and rhinitis (Control group). Materials and methods:In the retrospective case control study patients who are followed in our immunology and allergy clinic and to whom performed polysomnography because of any OSA releated symptoms were collected for AERD group. ATRD and control group were selected from polysomnography records. 15 patients with AERD group, 11 with ATRD group and 11 with control group were matched with age, sex, and body mass index (BMI). Results:In this study we have observed that AERD and ATRD groups have frequently OSA (40%, 72.2% respectively), but control group 18.18% have. Although mean FEV1 is lower in AERD group, reversly AHI is higher in ATRD group. In the group of AERD with aspirin desensitizated, OSA was seen in 22.22%; but in nondesensitizated goup OSA was seen in 66.66% patients (p=0.085). In the AERD group number of polypectomy operation and AHI were significantly correlated (p=0.001, r=0.74). Conclusion:To our best knowledge this is the first study demonstrated that AERD and OSA have been associated with each other; it seems to be affected by aspirin desesitization and number of nasal polypectomy operation.

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Increased urinary leukotriene E4 excretion in obstructive sleep apnea: Effects of obesity and hypoxia

Cited by 50 publications

References 34 publications

Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea

Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea

Sleep apnoea syndrome in 2011: current concepts and future directions

Is there any asociation between obstructive sleep apnea (OSA) and aspirin-exacerbated respiratory disease (AERD)? Does aspirin desensitization affect OSA risk?

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