|
1
|
Durdikova A, Durdik P, Prso M, Dvorska D, Remen L, Vojtkova J, Oleksak F, Banovcin P. Elastography as a non-invasive method of screening non-alcoholic fatty liver disease in the adult phenotype of paediatric obstructive sleep apnoea. Sleep Breath 2024; 28:2653-2661. [PMID: 39264533 PMCID: PMC11567998 DOI: 10.1007/s11325-024-03149-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 08/14/2024] [Accepted: 08/23/2024] [Indexed: 09/13/2024]
Abstract
PURPOSE The high prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children with obstructive sleep apnoea (OSA) calls for early non-invasive screening. The aim of this study was to use ultrasonographic liver echogenicity and elasticity to evaluate the early stages of liver injury in obese children with OSA. METHODS Fifty-five obese children with OSA aged 12 to 15 years were included. The control group (n = 56) consisted of healthy, non-obese children. All children underwent ultrasound examination to assess liver echogenicity using the hepatorenal index (HRI) and real-time elastography to determine the liver fibrosis index (LFI). Polysomnographic parameters, sonographic values, and clinical-biochemical assessment were statistically analysed according to OSA and its severity. Subgroup 1 was obese children with OSA and AHI < 5 and subgroup 2 was obese children with OSA and AHI ≥ 5. RESULTS Higher average values of HRI and LFI were recorded in the group of obese paediatric patients with OSA (mean age ± SD, 14.1 ± 2.2 year; 53% male; BMI z-score, 2.6 ± 0.35) compared to the control group (1.37 ± 0.19 vs. 1.12 ± 0.07, p < 0.001 and 1.82 ± 0.31 vs. 1.02 ± 0.27, p < 0.001). A significantly higher LFI was recorded in subgroup 2 compared to subgroup 1 (2.0 ± 0.3 vs. 1.6 ± 0.2, p < 0.001) while laboratory parameters and HRI (1.4 ± 0.2 vs. 1.4 ± 0.2, p = 0.630) did not change significantly. A strong positive correlation was found between the severity of OSA and the LFI (r = 0.454; p < 0.01). CONCLUSIONS These findings suggest that ultrasound elastography is a useful non-invasive screening test for OSA-related steatohepatitis in obese adolescents, but other clinical studies are needed to confirm this result.
Collapse
Affiliation(s)
- Anna Durdikova
- Paediatric Department, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, Martin, 036 01, Slovakia
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| | - Peter Durdik
- Paediatric Department, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, Martin, 036 01, Slovakia.
- Paediatric Department, University Hospital Martin, Martin, Slovakia.
| | - Marek Prso
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| | - Dominika Dvorska
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| | - Lukas Remen
- Paediatric Department, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, Martin, 036 01, Slovakia
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| | - Jarmila Vojtkova
- Paediatric Department, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, Martin, 036 01, Slovakia
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| | - Filip Oleksak
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| | - Peter Banovcin
- Paediatric Department, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, Martin, 036 01, Slovakia
- Paediatric Department, University Hospital Martin, Martin, Slovakia
| |
Collapse
|
|
2
|
Stadler S, Mohr A, Wagner A, Bäßler A, Fischer M, Putz FJ, Strack C, Li J, Arzt M. Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease. Sleep Med 2023; 112:159-164. [PMID: 37866211 DOI: 10.1016/j.sleep.2023.10.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 10/04/2023] [Accepted: 10/16/2023] [Indexed: 10/24/2023]
Abstract
INTRODUCTION Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. METHODS Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. RESULTS 48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. CONCLUSION Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.
Collapse
Affiliation(s)
- S Stadler
- Department of Internal Medicine II, University Hospital Regensburg, Germany.
| | - A Mohr
- Department of Pneumology, Clinic Donaustauf, Germany
| | - A Wagner
- Department of Internal Medicine II, University Hospital Regensburg, Germany
| | - A Bäßler
- Department of Internal Medicine II, University Hospital Regensburg, Germany
| | - M Fischer
- Department of Internal Medicine II, University Hospital Regensburg, Germany; Department of Internal Medicine II, Clinic Kelheim, Germany
| | - F J Putz
- Department of Nephrology, University Hospital Regensburg, Germany
| | - C Strack
- Department of Internal Medicine II, University Hospital Regensburg, Germany
| | - J Li
- Department of Cardiothoracic Surgery, University Hospital Regensburg, Germany
| | - M Arzt
- Department of Internal Medicine II, University Hospital Regensburg, Germany
| |
Collapse
|
|
3
|
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Although environmental factors are major contributors to early onset, children have both shared and unique genetic risk alleles as compared with adults with NAFLD. Treatment relies on reducing environmental risk factors, but many children have persistent diseases. No medications are approved specifically for the treatment of NAFLD, but some anti-obesity or diabetes treatments may be beneficial. Pediatric NAFLD increases the risk of diabetes and other cardiovascular risk factors. Long-term prospective studies are needed to determine the long-term risk of hepatic and non-hepatic morbidity and mortality in adulthood.
Collapse
Affiliation(s)
- Stavra A Xanthakos
- Professor of Pediatrics, Division of Gastroenterology Hepatology and Nutrition, Cincinnati Children's, Department of Pediatrics, Director, Nonalcoholic Steatohepatitis Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
| |
Collapse
|
|
4
|
Chi ZC. Research status and progress of metabolic associated fatty liver disease. Shijie Huaren Xiaohua Zazhi 2022; 30:1-16. [DOI: 10.11569/wcjd.v30.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a more appropriate general predicate to describe non-alcoholic fatty liver disease. The new definition lists metabolic dysfunction as an important cause of liver disease, demonstrates the high heterogeneity of this condition, and speeds up the transformation path to new treatment. The incidence of extrahepatic complications and related diseases of MAFLD far exceed that of the liver disease itself, which seriously threatens human health. In view of the current insufficient understanding of its severity, and the imperfect understanding of the disease scope, pathogenesis, and diagnosis of extrahepatic complications, especially the lack of effective drug treatment, this paper introduces and reviews the research status and progress of extrahepatic complications of MAFLD.
Collapse
Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
| |
Collapse
|
|
5
|
Carotenuto M, Di Sessa A, Esposito M, Grandone A, Marzuillo P, Bitetti I, Umano GR, Precenzano F, Miraglia del Giudice E, Santoro N. Association between Hepatic Steatosis and Obstructive Sleep Apnea in Children and Adolescents with Obesity. CHILDREN (BASEL, SWITZERLAND) 2021; 8:984. [PMID: 34828697 PMCID: PMC8624374 DOI: 10.3390/children8110984] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 04/09/2023]
Abstract
BACKGROUND Owing to the increasing rate of pediatric obesity, its complications such as non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) have become prevalent already in childhood. We aimed to assess the relationship between these two diseases in a cohort of children with obesity. METHODS We enrolled 153 children with obesity (mean age 10.5 ± 2.66, mean BMI 30.9 ± 5.1) showing OSA. Subjects underwent a laboratory evaluation, a cardio-respiratory polysomnography (PSG), and a liver ultrasound. RESULTS All subjects had a clinical diagnosis of OSA based on the AHI > 1/h (mean AHI 8.0 ± 5.9; range 2.21-19.0). Of these, 69 showed hepatic steatosis (62.3% as mild, 20.3% as moderate, and 17.4% as severe degree). A strong association between ALT and apnea/hypopnea index (AHI) was observed (p = 0.0003). This association was not confirmed after adjusting for hepatic steatosis (p = 0.53). By subdividing our population according to the presence/absence of steatosis, this association was found only in the steatosis group (p = 0.009). As the severity of steatosis increased, the significance of its association with AHI compared to the absence of steatosis became progressively stronger (all p < 0.0001). CONCLUSIONS Hepatic steatosis seems to drive the association between OSA and ALT levels, suggesting a potential pathogenic role of OSA in NAFLD.
Collapse
Affiliation(s)
- Marco Carotenuto
- Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (M.C.); (M.E.); (I.B.); (F.P.)
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.G.); (P.M.); (G.R.U.); (E.M.d.G.)
| | - Maria Esposito
- Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (M.C.); (M.E.); (I.B.); (F.P.)
| | - Anna Grandone
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.G.); (P.M.); (G.R.U.); (E.M.d.G.)
| | - Pierluigi Marzuillo
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.G.); (P.M.); (G.R.U.); (E.M.d.G.)
| | - Ilaria Bitetti
- Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (M.C.); (M.E.); (I.B.); (F.P.)
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.G.); (P.M.); (G.R.U.); (E.M.d.G.)
| | - Francesco Precenzano
- Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy; (M.C.); (M.E.); (I.B.); (F.P.)
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.G.); (P.M.); (G.R.U.); (E.M.d.G.)
| | - Nicola Santoro
- Department of Pediatrics, Yale University, New Haven, CT 06510, USA;
- Department of Medicine and Health Sciences, “V.Tiberio” University of Molise, 86100 Campobasso, Italy
| |
Collapse
|
|
6
|
Ulland TK, Ewald AC, Knutson AO, Marino KM, Smith SMC, Watters JJ. Alzheimer's Disease, Sleep Disordered Breathing, and Microglia: Puzzling out a Common Link. Cells 2021; 10:2907. [PMID: 34831129 PMCID: PMC8616348 DOI: 10.3390/cells10112907] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 10/22/2021] [Accepted: 10/24/2021] [Indexed: 12/14/2022] Open
Abstract
Sleep Disordered Breathing (SDB) and Alzheimer's Disease (AD) are strongly associated clinically, but it is unknown if they are mechanistically associated. Here, we review data covering both the cellular and molecular responses in SDB and AD with an emphasis on the overlapping neuroimmune responses in both diseases. We extensively discuss the use of animal models of both diseases and their relative utilities in modeling human disease. Data presented here from mice exposed to intermittent hypoxia indicate that microglia become more activated following exposure to hypoxia. This also supports the idea that intermittent hypoxia can activate the neuroimmune system in a manner like that seen in AD. Finally, we highlight similarities in the cellular and neuroimmune responses between SDB and AD and propose that these similarities may lead to a pathological synergy between SDB and AD.
Collapse
Affiliation(s)
- Tyler K. Ulland
- Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53705, USA; (T.K.U.); (K.M.M.)
- Neuroscience Training Program, University of Wisconsin Madison, Madison, WI 53705, USA
| | - Andrea C. Ewald
- Department of Comparative Biosciences, University of Wisconsin Madison, Madison, WI 53706, USA; (A.C.E.); (A.O.K.); (S.M.C.S.)
| | - Andrew O. Knutson
- Department of Comparative Biosciences, University of Wisconsin Madison, Madison, WI 53706, USA; (A.C.E.); (A.O.K.); (S.M.C.S.)
| | - Kaitlyn M. Marino
- Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53705, USA; (T.K.U.); (K.M.M.)
- Neuroscience Training Program, University of Wisconsin Madison, Madison, WI 53705, USA
| | - Stephanie M. C. Smith
- Department of Comparative Biosciences, University of Wisconsin Madison, Madison, WI 53706, USA; (A.C.E.); (A.O.K.); (S.M.C.S.)
| | - Jyoti J. Watters
- Neuroscience Training Program, University of Wisconsin Madison, Madison, WI 53705, USA
- Department of Comparative Biosciences, University of Wisconsin Madison, Madison, WI 53706, USA; (A.C.E.); (A.O.K.); (S.M.C.S.)
| |
Collapse
|
|
7
|
The association between obstructive sleep apnea and non-alcoholic steatohepatitis: a retrospective nationwide inpatient sample analysis. Clin Exp Hepatol 2021; 7:25-29. [PMID: 34027112 PMCID: PMC8122103 DOI: 10.5114/ceh.2021.104488] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 10/24/2020] [Indexed: 12/13/2022] Open
Abstract
Aim of the study The primary purpose of this study was to assess the association of obstructive sleep apnea (OSA) and non-alcoholic steatohepatitis (NASH) from a large national inpatient sample database. Material and methods We conducted a retrospective analysis using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. OSA and NASH patients were identified using the ICD-10-CM code G47.33 and K75.81. Non-NASH patients (control) were randomly selected and matched by age and gender to each NASH patient in a 4 : 1 ratio. Weighted logistic regression models were used to calculate the association between OSA and NASH in addition to different comorbidities. Results A total of 54,169 participants were included in our analysis; 10,740 cases of NASH were matched to 43,429 controls (non-NASH). NASH was significantly higher in the white population (82.12% vs. 76.64%, p < 0.001). The prevalence of OSA among NASH patients was significantly higher compared to the control group (15.8% vs. 8.9%, adjusted OR: 1.34, 95% CI: 1.14-1.56, p = 0.0003). The prevalence of celiac disease and Crohn’s disease was significantly higher in patients with NASH (0.7% vs. 0.2%, p < 0.0002 and 1.28% vs. 0.76%, p < 0.0001). Multiple comorbidities were significantly elevated in the NASH group compared to the non-NASH group, including diabetes mellitus (DM; 36% vs. 17.6%, p < 0.0001), obesity (36.4% vs. 18.2%, p < 0.0001) and metabolic syndrome (0.86% vs. 0.06%, p < 0.0001). The mortality rate was significantly higher in the NASH group (3.8% vs. 2%, p < 0.0001). Conclusions This is the first study using the ICD-10-CM code with a specific search code for NASH. Our large population database results emphasize that there is a significant association between OSA and NASH.
Collapse
|
|
8
|
Chen LD, Chen MX, Chen GP, Lin XJ, Huang JF, Zeng AM, Huang YP, Lin QC. Association between obstructive sleep apnea and non-alcoholic fatty liver disease in pediatric patients: a meta-analysis. Pediatr Obes 2021; 16:e12718. [PMID: 32881371 DOI: 10.1111/ijpo.12718] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/02/2020] [Accepted: 08/07/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Some studies have reported a relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in pediatric population. However, this issue remains controversial. OBJECTIVES The purpose of the present study was to investigate the association between OSA and NAFLD in pediatric population. METHODS We systematically searched PubMed, Web of Science, Embase for eligible studies. The data involving markers of NAFLD including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic inflammation, hepatic fibrosis of both OSA group and control group were extracted. Pooled standardised mean difference (SMD) and weighted mean difference (WMD) were appropriately calculated through a fixed or random-effect model. RESULTS Nine cross-sectional studies with 1133 children and adolescents were included. OSA was significantly associated with ALT, AST, and NAFLD fibrosis stage, but not NAFLD inflammation grade. Subgroup analysis indicated that both mild OSA and severe OSA were significantly associated with elevated ALT and AST. Furthermore, in the studies with all main confounding factors (age, gender, and BMI) matched, OSA group had higher ALT and AST levels than control group. CONCLUSIONS This meta-analysis suggested that OSA was associated with NAFLD evidenced by elevated liver enzymes and progressive hepatic fibrosis in pediatric population. Screening and monitoring of NAFLD in pediatric patients with obesity-related OSA are necessary.
Collapse
Affiliation(s)
- Li-Da Chen
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Meng-Xue Chen
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Gong-Ping Chen
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xue-Jun Lin
- Department of Laboratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Jie-Feng Huang
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ai-Ming Zeng
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ya-Ping Huang
- Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Qi-Chang Lin
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Provincial Sleep-disordered Breathing Clinic Center, Fuzhou, China.,Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, China
| |
Collapse
|
|
9
|
Orr WC, Fass R, Sundaram SS, Scheimann AO. The effect of sleep on gastrointestinal functioning in common digestive diseases. Lancet Gastroenterol Hepatol 2020; 5:616-624. [DOI: 10.1016/s2468-1253(19)30412-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/25/2019] [Accepted: 11/12/2019] [Indexed: 02/07/2023]
|
|
10
|
Savini S, Ciorba A, Bianchini C, Stomeo F, Corazzi V, Vicini C, Pelucchi S. Assessment of obstructive sleep apnoea (OSA) in children: an update. ACTA ACUST UNITED AC 2020; 39:289-297. [PMID: 31708576 PMCID: PMC6843580 DOI: 10.14639/0392-100x-n0262] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 08/11/2019] [Indexed: 02/04/2023]
Abstract
OSA is a condition characterised by episodes of complete or partial obstruction of the upper airway, associated with blood-gas changes and atypical sleep patterns. Early diagnosis of OSA may reduce the occurrence of systemic complications over time, although the diagnosis of OSA is, unfortunately, often late. The aim of the work is to review the current concepts in evaluation of paediatric obstructive sleep apnoea (OSA), with an updated revision of the literature considering risk factors, clinical manifestations, and basic and advanced assessment in the paediatric population. For this narrative review, PubMed, Embase and Cinahl databases were searched for the last 10 years, according to PRISMA criteria/guidelines. Assessment of paediatric OSA remains challenging and paediatric patients should always be carefully evaluated; polysomnography is the gold standard for diagnosis of paediatric OSA.
Collapse
Affiliation(s)
- S Savini
- ENT Department, University Hospital of Ferrara, Italy
| | - A Ciorba
- ENT Department, University Hospital of Ferrara, Italy
| | - C Bianchini
- ENT Department, University Hospital of Ferrara, Italy
| | - F Stomeo
- ENT Department, University Hospital of Ferrara, Italy
| | - V Corazzi
- ENT Department, University Hospital of Ferrara, Italy
| | - C Vicini
- Head-Neck and Oral Surgery Unit, Morgagni Pierantoni Hospital, Azienda USL della Romagna, Forlì, Italy
| | - S Pelucchi
- ENT Department, University Hospital of Ferrara, Italy
| |
Collapse
|
|
11
|
Gozal D, Tan HL, Kheirandish-Gozal L. Treatment of Obstructive Sleep Apnea in Children: Handling the Unknown with Precision. J Clin Med 2020; 9:jcm9030888. [PMID: 32213932 PMCID: PMC7141493 DOI: 10.3390/jcm9030888] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/06/2020] [Accepted: 03/18/2020] [Indexed: 12/18/2022] Open
Abstract
Treatment approaches to pediatric obstructive sleep apnea (OSA) have remarkably evolved over the last two decades. From an a priori assumption that surgical removal of enlarged upper airway lymphadenoid tissues (T&A) was curative in the vast majority of patients as the recommended first-line treatment for pediatric OSA, residual respiratory abnormalities are frequent. Children likely to manifest persistent OSA after T&A include those with severe OSA, obese or older children, those with concurrent asthma or allergic rhinitis, children with predisposing oropharyngeal or maxillomandibular factors, and patients with underlying medical conditions. Furthermore, selection anti-inflammatory therapy or orthodontic interventions may be preferable in milder cases. The treatment options for residual OSA after T&A encompass a large spectrum of approaches, which may be complementary, and clearly require multidisciplinary cooperation. Among these, continuous positive airway pressure (CPAP), combined anti-inflammatory agents, rapid maxillary expansion, and myofunctional therapy are all part of the armamentarium, albeit with currently low-grade evidence supporting their efficacy. In this context, there is urgent need for prospective evidence that will readily identify the correct candidate for a specific intervention, and thus enable some degree of scientifically based precision in the current one approach fits all model of pediatric OSA medical care.
Collapse
Affiliation(s)
- David Gozal
- Department of Child Health and the Child Health Research Institute, University of Missouri School of Medicine, Columbia, MO 65201, USA;
- Correspondence:
| | - Hui-Leng Tan
- Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK;
| | - Leila Kheirandish-Gozal
- Department of Child Health and the Child Health Research Institute, University of Missouri School of Medicine, Columbia, MO 65201, USA;
| |
Collapse
|
|
12
|
Tomkies A, Johnson RF, Shah G, Caraballo M, Evans P, Mitchell RB. Obstructive Sleep Apnea in Children With Autism. J Clin Sleep Med 2019; 15:1469-1476. [PMID: 31596212 PMCID: PMC6778353 DOI: 10.5664/jcsm.7978] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 06/04/2019] [Accepted: 06/04/2019] [Indexed: 11/13/2022]
Abstract
STUDY OBJECTIVES To describe the demographic and clinical characteristics of children with autism spectrum disorder (ASD) referred for polysomnography (PSG) and to look for predictors of obstructive sleep apnea (OSA) and severe OSA in these children. METHODS This is a retrospective case series of children ages 2 to 18 years who underwent PSG between January 2009 and February 2015. Children were excluded if they had major comorbidities, prior tonsillectomy, or missing data. The following information was collected: age, sex, race, height, weight, tonsil size, and prior diagnosis of allergies, asthma, gastroesophageal reflux disease, seizure disorder, developmental delay, cerebral palsy, or attention deficit hyperactivity disorder. Predictors of OSA were evaluated. RESULTS A total of 45 children were included with a mean (standard deviation [SD]) age of 6.1 years (2.8). The patients were 80% male, 49% Hispanic, 27% African American, 22% Caucasian, and 2.2% other. Of these children 26 (58%) had OSA (apnea-hypopnea index [AHI] > 1 event/h) and 15 (33%) were obese (body mass index, body mass index z-score ≥ 95th percentile). The mean (SD) AHI was 7.7 (15.0) events/h (range 1.0-76.6). A total of 9 (20%) had severe OSA (AHI ≥ 10 events/h). There were no demographic or clinical predictors of OSA in this group. However, increasing weight served as a predictor of severe OSA and African American or Hispanic children were more likely obese. CONCLUSIONS The absence of demographic or clinical predictors of OSA supports using general indications for PSG in children with ASD.
Collapse
Affiliation(s)
- Anna Tomkies
- Division of Pediatric Otolaryngology, Department of Otolaryngology, Head and Neck Surgery, University of Texas Southwestern Medical Center and Children’s Health, Dallas, Texas
| | - Romaine F. Johnson
- Division of Pediatric Otolaryngology, Department of Otolaryngology, Head and Neck Surgery, University of Texas Southwestern Medical Center and Children’s Health, Dallas, Texas
| | - Gopi Shah
- Division of Pediatric Otolaryngology, Department of Otolaryngology, Head and Neck Surgery, University of Texas Southwestern Medical Center and Children’s Health, Dallas, Texas
| | - Michelle Caraballo
- Division of Respiratory Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center and Children’s Health, Dallas, Texas
| | - Patricia Evans
- Division of Neurology, Department of Pediatrics, University of Texas Southwestern Medical Center and Children’s Health, Dallas, Texas
| | - Ron B. Mitchell
- Division of Pediatric Otolaryngology, Department of Otolaryngology, Head and Neck Surgery, University of Texas Southwestern Medical Center and Children’s Health, Dallas, Texas
| |
Collapse
|
|
13
|
Chen T, Hughes ME, Wang H, Wang G, Hong X, Liu L, Ji Y, Pearson C, Li S, Hao L, Wang X. Prenatal, Perinatal, and Early Childhood Factors Associated with Childhood Obstructive Sleep Apnea. J Pediatr 2019; 212:20-27.e10. [PMID: 31253409 PMCID: PMC6707868 DOI: 10.1016/j.jpeds.2019.05.053] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 05/07/2019] [Accepted: 05/21/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To investigate prenatal, perinatal, and early childhood factors, including cord and early childhood plasma leptin, on a clinical diagnosis of obstructive sleep apnea (OSA) among children in the Boston Birth Cohort. STUDY DESIGN We conducted a secondary analysis of 2867 mother-child pairs from the Boston Birth Cohort who were enrolled between 1998 and 2014 at Boston Medical Center and followed from birth to age 16 years. Child's OSA was defined based on clinical diagnoses documented in the medical record. Plasma leptin was measured in cord and early childhood blood samples. Logistic regression was used to examine individual and combined effects of early life factors on the risk of OSA, adjusting for potential confounders. RESULTS The mean age of the study children was 6.39 years (SD = 3.77); 49.3% were girls, and 209 (7.3%) had ever been diagnosed with OSA. Four significant risk factors for OSA were identified: maternal obesity/diabetes during pregnancy (OR, 1.63; 95% CI, 1.21-2.21; P = .001), preterm/low birth weight (OR, 1.74; 95% CI, 1.30-2.32; P < .001), early childhood obesity (OR, 1.89; 95% CI, 1.37-2.62; P < .001), and high leptin levels in early childhood (OR, 1.94; 95% CI, 1.22-3.09; P = .005). The presence of all these 4 risk factors significantly amplified the odds of OSA by about 10 times (OR, 9.95; 95% CI, 3.42-28.93; P < .001) compared with those lacking these factors. CONCLUSIONS Our findings, if further confirmed, provide new insight into the early life risk factors of pediatric OSA and underscore the need for early screening and prevention of OSA among children with those risk factors.
Collapse
Affiliation(s)
- Ting Chen
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Mary E Hughes
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Hongjian Wang
- National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guoying Wang
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Xiumei Hong
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Li Liu
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Yuelong Ji
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Colleen Pearson
- Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA
| | - Shenghui Li
- Department of Preventive Medicine, Jiao Tong University School of Medicine, Shanghai, China
| | - Lingxin Hao
- Hopkins Population Center, Johns Hopkins University, Baltimore, MD
| | - Xiaobin Wang
- Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
| |
Collapse
|
|
14
|
A Systematic Review of NAFLD-Associated Extrahepatic Disorders in Youths. J Clin Med 2019; 8:jcm8060868. [PMID: 31213030 PMCID: PMC6617181 DOI: 10.3390/jcm8060868] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 06/04/2019] [Accepted: 06/13/2019] [Indexed: 02/07/2023] Open
Abstract
Background: There is growing evidence that non-alcoholic fatty liver disease (NAFLD) is a disease affecting not only the liver but also extrahepatic organs. Aim: To investigate whether in youths NAFLD is associated with extrahepatic complications such as subclinical atherosclerosis, cardiac abnormalities, hypertension, type 2 diabetes, decreased bone mineral density, renal dysfunction, obstructive sleep apnea, and polycystic ovary syndrome. Methods: We systematically reviewed PubMed; Scopus; Embase; and the Cochrane Library databases up to 28 February 2019 and assessed the quality of studies using the Newcastle-Ottawa Scale. Results: Thirty-five articles were selected for this systematic review: fifteen (4627 participants) evaluated the association of NAFLD with subclinical atherosclerosis; four (969 participants) with cardiac abnormalities; two (550 participants) with hypertension; four (1328 participants) with diabetes; six (523 participants) with low bone mineral density; two (865 participants) with renal dysfunction; one with obstructive sleep apnea; and one with polycystic ovary syndrome. Most studies found that youths with NAFLD have increased features of subclinical atherosclerosis; as well as of cardiac alterations. Limited data were available to endorse a solid estimate of the prevalence of diabetes; low mineral density and renal dysfunction in the pediatric NAFLD population. Conclusion: NAFLD-related intermediate CVD outcomes can occur and be detected early in young populations.
Collapse
|
|
15
|
Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children. J Pediatr 2018; 198:67-75.e1. [PMID: 29752170 DOI: 10.1016/j.jpeds.2018.03.028] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 02/27/2018] [Accepted: 03/14/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress. STUDY DESIGN Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes. RESULTS Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m2) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes. CONCLUSIONS This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia.
Collapse
|
|
16
|
Labarca G, Cruz R, Jorquera J. Continuous Positive Airway Pressure in Patients With Obstructive Sleep Apnea and Non-Alcoholic Steatohepatitis: A Systematic Review and Meta-Analysis. J Clin Sleep Med 2018; 14:133-139. [PMID: 29151428 DOI: 10.5664/jcsm.6900] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 09/14/2017] [Indexed: 12/13/2022]
Abstract
STUDY OBJECTIVES Several studies have reported an association between obstructive sleep apnea (OSA) and several extra-pulmonary issues, such as arterial hypertension and insulin resistance. In recent years, the associations between OSA, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis (NASH) have been published; however, there is a gap between experimental and clinical studies regarding the efficacy of continuous positive airway pressure (CPAP) treatment in patient populations with these conditions. This issue should be considered when deciding on CPAP treatment in patients with OSA, especially in patients with moderate OSA. METHODS We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) using the following databases: MEDLINE, Lilacs, and CENTRAL. Two independent reviewers performed the search, analysis, data extraction, and critical analysis. RESULTS From 622 identified studies, we included 5 RCTs that involved patients with OSA and NASH and who were treated with a CPAP device. After CPAP treatment, no changes in liver steatosis, liver fibrosis, and aminotransferase levels (alanine aminotransferase and aspartate aminotransferase) were found. Finally, the quality of evidence using the GRADE approach was low and very low for several outcomes. CONCLUSIONS According to the current analysis, no data regarding the efficacy of CPAP in patients with NASH are available to make recommendations. SYSTEMATIC REVIEW REGISTRATION PROSPERO; ID: CRD42015027981; URL: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42015027981.
Collapse
Affiliation(s)
- Gonzalo Labarca
- Universidad San Sebastián, Concepción, Chile.,Departamento de Medicina Interna, Complejo Asistencial Víctor Ríos Ruiz, Los Ángeles, Chile
| | - Rodrigo Cruz
- Gastroenterology, Hospital Dipreca, Santiago, Chile
| | - Jorge Jorquera
- Sleep Center and Respiratory Disease, Clinica Las Condes, Santiago, Chile
| |
Collapse
|
|
17
|
Liu X, Miao Y, Wu F, Du T, Zhang Q. Effect of CPAP therapy on liver disease in patients with OSA: a review. Sleep Breath 2018; 22:963-972. [PMID: 29327118 DOI: 10.1007/s11325-018-1622-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 12/15/2017] [Accepted: 01/05/2018] [Indexed: 12/15/2022]
Abstract
Obstructive sleep apnea (OSA) may play an important role in the progression of nonalcoholic fatty liver disease (NAFLD).The effect of continuous positive airway pressure (CPAP) treatment, the first-line therapy for OSA, on liver disease in OSA patients is still debated. We provide this review of previous studies to summarize the effects of CPAP treatment on liver disease in OSA patients in aspects of liver function, liver steatosis, fibrosis, and incidence of liver disease. CPAP treatment may be beneficial to liver disease in subjects with OSA independent of metabolic risk factors, but a sufficiently long therapeutic duration (perhaps greater than 3 months) may be needed to achieve these positive effects. Though the mechanism of impact of CPAP treatment on liver in OSA patients is unclear, the influence of CPAP treatment on the factors of the "Two-hit" hypothesis (insulin resistance, fatty acids dysregulation, oxidative stress, and inflammation) may be a reasonable explanation.
Collapse
Affiliation(s)
- Xin Liu
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | | | - Fan Wu
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Tingting Du
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China
| | - Qiang Zhang
- Institute of Gerontology of Tianjin, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping District, Tianjin, China.
| |
Collapse
|
|
18
|
Chen LD, Lin L, Zhang LJ, Zeng HX, Wu QY, Hu MF, Xie JJ, Liu JN. Effect of continuous positive airway pressure on liver enzymes in obstructive sleep apnea: A meta-analysis. CLINICAL RESPIRATORY JOURNAL 2016; 12:373-381. [PMID: 27614004 DOI: 10.1111/crj.12554] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 08/07/2016] [Accepted: 08/29/2016] [Indexed: 12/25/2022]
Abstract
BACKGROUND Previous studies have suggested that obstructive sleep apnea (OSA) was associated with nonalcoholic fatty liver disease (NAFLD). However, the impact of OSA treatment using continuous positive airway pressure (CPAP) on liver enzymes remained controversial. This meta-analysis was conducted to determine whether CPAP therapy could reduce liver enzyme levels. METHODS Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before December 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum ALT and AST was extracted for analysis. A total of five studies with seven cohorts that included 192 patients were pooled into meta-analysis. RESULTS CPAP was associated with a statistically significant decrease on both ALT and AST levels in OSA patients (WMD = 8.036, 95% CI = 2.788-13.285, z = 3.00, P = .003 and WMD = 4.612, 95% CI = 0.817-8.407, z = 2.38, P = .017, respectively). Subgroup analyses indicated that CPAP therapy was more effective in OSA patients with treatment duration > 3 mo (WMD = 12.374, 95% CI = 2.727-22.020, z = 2.51, P = .012 for ALT and WMD = 7.576, 95% CI = 1.781-13.370, z =2.56, P = .010 for AST). CONCLUSION This meta-analysis suggested that CPAP was associated with a statistically significant decrease on liver enzymes in OSA patients. Further large-scale well-designed RCTs with long-term follow-up are required to clarify this issue.
Collapse
Affiliation(s)
- Li-Da Chen
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Li Lin
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Liang-Ji Zhang
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Hui-Xue Zeng
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Qi-Yin Wu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Miao-Feng Hu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Jian-Jun Xie
- Department of Radiation Oncology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| | - Jian-Nan Liu
- Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, People's Republic of China
| |
Collapse
|
|
19
|
Aron-Wisnewsky J, Clement K, Pépin JL. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism 2016; 65:1124-35. [PMID: 27324067 DOI: 10.1016/j.metabol.2016.05.004] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 05/03/2016] [Accepted: 05/07/2016] [Indexed: 12/18/2022]
Abstract
Obstructive sleep apnea (OSA) and more importantly its hallmark, chronic intermittent hypoxia (CIH), are established factors in the pathogenesis and exacerbation of nonalcoholic fatty liver disease (NAFLD). This has been clearly demonstrated in rodent models exposed to intermittent hypoxia, and strong evidence now also exists in both paediatric and adult human populations. OSA and CIH induce insulin-resistance and dyslipidemia which are involved in NAFLD physiopathogenesis. CIH increases the expression of the hypoxia inducible transcription factor HIF1α and that of downstream genes involved in lipogenesis, thereby increasing β-oxidation and consequently exacerbating liver oxidative stress. OSA also disrupts the gut liver axis, increasing intestinal permeability and with a possible role of gut microbiota in the link between OSA and NAFLD. OSA patients should be screened for NAFLD and vice versa those with NAFLD for OSA. To date there is no evidence that treating OSA with continuous positive airway pressure (CPAP) will improve NAFLD but it might at least stabilize and slow its progression. Nevertheless, these multimorbid patients should be efficiently treated for all their metabolic co-morbidities and be encouraged to follow weight stabilization or weight loss programs and physical activity life style interventions.
Collapse
Affiliation(s)
- Judith Aron-Wisnewsky
- Institute of Cardiometabolism and Nutrition, ICAN, Assistance Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR_S U1166, Nutriomics, 75013 Paris, France; INSERM, UMR_S U1166, Nutriomics, 75013 Paris, France.
| | - Karine Clement
- Institute of Cardiometabolism and Nutrition, ICAN, Assistance Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR_S U1166, Nutriomics, 75013 Paris, France; INSERM, UMR_S U1166, Nutriomics, 75013 Paris, France
| | - Jean-Louis Pépin
- Institut National de la Santé et de la Recherche Médicale (INSERM), U 1042, HP2 Laboratory (Hypoxia: Pathophysiology), Grenoble Alpes Univ., Grenoble, F-38000, France;; Grenoble Alpes University Hospital, Pole Thorax et Vaisseaux, F-38000, France.
| |
Collapse
|
|
20
|
Pediatric Sleep Apnea Syndrome: An Update. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2016; 4:852-61. [PMID: 27372597 DOI: 10.1016/j.jaip.2016.02.022] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 02/17/2016] [Accepted: 02/26/2016] [Indexed: 01/04/2023]
Abstract
Obstructive sleep apnea syndrome (OSAS) may be central neurologic (<5%) or obstructive (>95%) in origin and is a relatively prevalent condition in children. It affects 1%-5% of children aged 2-8 years and is caused by a variety of different pathophysiologic abnormalities. Cardiovascular, metabolic, and neurocognitive comorbidities can occur in both children and adults when left untreated. It also can cause severe behavioral problems in children. The American Academy of Pediatrics recommends that all children be screened with an appropriate history and physical examination for symptoms and signs suggestive of OSAS. The diagnosis is primarily made clinically and confirmed by polysomnographic findings. Treatment depends on the child's age, underlying medical problems, polysomnography findings, and whether or not there is upper airway obstruction usually secondary to enlarged adenoids and/or tonsils, allergic and nonallergic rhinitis, acute and chronic sinusitis, and other upper airway pathology. If enlarged adenoid or tonsils or both conditions exist, an adenoidectomy, tonsillectomy, or adenotonsillectomy remains the treatment of choice. Pharmacotherapy of OSAS has shown some effect in children with mild symptoms. This paper reviews the prevalence, pathophysiology, clinical presentation, diagnosis, and treatment of OSAS.
Collapse
|
|
21
|
Kheirandish-Gozal L, Philby MF, Alonso-Álvarez ML, Terán-Santos J, Gozal D. Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy. Sleep 2016; 39:1225-32. [PMID: 27070140 DOI: 10.5665/sleep.5838] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 03/02/2016] [Indexed: 11/03/2022] Open
Abstract
STUDY OBJECTIVE Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid β protein 42 (Aβ42) and pre-senilin 1 (PS1). METHODS Fasting morning plasma samples from otherwise healthy children with a diagnosis of OB, OSA, or both (OSA+OB), and controls, and in a subset of children with OSA after adenotonsillectomy (T&A) were assayed for Aβ42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits. RESULTS 286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar Aβ42 (108.3 ± 31.7 pg/mL versus 83.6 ± 14.6 pg/mL) and PS1 levels (0.89 ± 0.44 ng/mL versus 0.80 ± 0.29 pg/mL). However, OSA children (Aβ42: 186.2 ± 66.7 pg/mL; P < 0.001; PS1: 3.42 ± 1.46 ng/mL; P < 0.001), and particularly OSA+OB children had significant elevations in both Aβ42 (349.4 ± 112.9 pg/mL; P < 0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P < 0.001) circulating concentrations. In a subset of 24 children, T&A resulted in significant reductions of Aβ42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P < 0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P < 0.0001). CONCLUSIONS Thus, OSA, and particularly OSA+OB, are associated with increased plasma levels of AD biomarkers, which decline upon treatment of OSA in a representative, yet not all- encompassing subset of patients, suggesting that OSA may accelerate AD-related processes even in early childhood. However, the cognitive and overall health-related implications of these findings remain to be defined.
Collapse
Affiliation(s)
- Leila Kheirandish-Gozal
- Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL
| | - Mona F Philby
- Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL
| | - María Luz Alonso-Álvarez
- Sleep Unit, CIBER of Respiratory Diseases, Instituto Carlos III, CIBERES, Hospital Universitario de Burgos (HUBU), Burgos, Spain
| | - Joaquin Terán-Santos
- Sleep Unit, CIBER of Respiratory Diseases, Instituto Carlos III, CIBERES, Hospital Universitario de Burgos (HUBU), Burgos, Spain
| | - David Gozal
- Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL
| |
Collapse
|
|
22
|
Gileles-Hillel A, Kheirandish-Gozal L, Gozal D. Biological plausibility linking sleep apnoea and metabolic dysfunction. Nat Rev Endocrinol 2016; 12:290-8. [PMID: 26939978 DOI: 10.1038/nrendo.2016.22] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Obstructive sleep apnoea (OSA) is a very common disorder that affects 10-25% of the general population. In the past two decades, OSA has emerged as a cardiometabolic risk factor in both paediatric and adult populations. OSA-induced metabolic perturbations include dyslipidaemia, atherogenesis, liver dysfunction and abnormal glucose metabolism. The mainstay of treatment for OSA is adenotonsillectomy in children and continuous positive airway pressure therapy in adults. Although these therapies are effective at resolving the sleep-disordered breathing component of OSA, they do not always produce beneficial effects on metabolic function. Thus, a deeper understanding of the underlying mechanisms by which OSA influences metabolic dysfunction might yield improved therapeutic approaches and outcomes. In this Review, we summarize the evidence obtained from animal models and studies of patients with OSA of potential mechanistic pathways linking the hallmarks of OSA (intermittent hypoxia and sleep fragmentation) with metabolic dysfunction. Special emphasis is given to adipose tissue dysfunction induced by sleep apnoea, which bears a striking resemblance to adipose dysfunction resulting from obesity. In addition, important gaps in current knowledge and promising lines of future investigation are identified.
Collapse
Affiliation(s)
- Alex Gileles-Hillel
- Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Knapp Center for Biomedical Discovery, Room 4100, 900 East 57th Street, Mailbox 4, Chicago, Illinois 60637-1470, USA
| | - Leila Kheirandish-Gozal
- Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Knapp Center for Biomedical Discovery, Room 4100, 900 East 57th Street, Mailbox 4, Chicago, Illinois 60637-1470, USA
| | - David Gozal
- Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Knapp Center for Biomedical Discovery, Room 4100, 900 East 57th Street, Mailbox 4, Chicago, Illinois 60637-1470, USA
| |
Collapse
|
|
23
|
Kawamura Y, Arase Y, Ikeda K, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Inao M, Mochida S, Kumada H. Effects of Alcohol Consumption on Hepatocarcinogenesis in Japanese Patients With Fatty Liver Disease. Clin Gastroenterol Hepatol 2016; 14:597-605. [PMID: 26707683 DOI: 10.1016/j.cgh.2015.11.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 11/30/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of ethanol consumption on hepatocarcinogenesis in patients with fatty liver disease (FLD) is not clear. We aimed to investigate the influence of alcohol consumption on hepatocarcinogenesis and determine the risk factors for hepatocellular carcinoma (HCC) in a large number of Japanese patients with FLD without viral hepatitis. METHODS This multicenter, retrospective cohort study was conducted at a specialized center for hepatology in Japan and included 9959 patients with FLD without viral hepatitis, diagnosed by ultrasonography from January 1997 through December 2011. The patients' level of ethanol consumption was divided into 4 categories: <20 g/day (n = 6671), 20-39 g/day (n = 753), 40-69 g/day (n = 1589), and ≥70 g/day (n = 946). The primary endpoint was the onset of HCC. Statistical analyses performed included the Kaplan-Meier method and Cox proportional hazard analysis. The median follow-up period was 5.4 years. RESULTS Of the study cohort, 49 cases (0.49%) developed HCC during the follow-up period. The annual incidence rate of HCC was 0.05% in patients with FLD and a daily ethanol consumption <20 g/day. Increasing levels of ethanol consumption were associated with increased annual incidence rates of HCC: 0.06% for patients with 20-39 g/day ethanol consumption (hazard ratio [HR], 1.54; 95% confidence interval [CI], 0.34-7.04), 0.16% for patients with 40-69 g/day ethanol consumption (HR, 3.49; 95% CI, 1.50-8.12), and 0.22% for patients with ≥70 g/day ethanol consumption (HR, 10.58; 95% CI, 5.06-22.13), compared with patients with ethanol consumption <20 g/day. Multivariate analysis showed that ethanol consumption ≥40 g/day was an independent risk factor for HCC: for 40-69 g/day the HR was 2.48 (95% CI, 1.01-6.05; P < .047) and for ≥70 g/day the HR was 12.61 (95% CI, 5.68-28.00; P < .001). CONCLUSIONS Based on a multicenter, retrospective analysis of almost 10,000 patients with FLD, ethanol consumption ≥40 g/day is an independent risk factor for HCC.
Collapse
Affiliation(s)
- Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Health Management Center, Toranomon Hospital, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Mie Inao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| |
Collapse
|
|
24
|
Arısoy A, Sertoğullarından B, Ekin S, Özgökçe M, Bulut MD, Huyut MT, Ölmez Ş, Turan M. Sleep Apnea and Fatty Liver Are Coupled Via Energy Metabolism. Med Sci Monit 2016; 22:908-13. [PMID: 26993969 PMCID: PMC4805136 DOI: 10.12659/msm.898214] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by intermittent hypoxia. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. We aimed to evaluate the relationship between OSA and fatty liver. MATERIAL/METHODS We enrolled 176 subjects to this study who underwent polysomnography (PSG) for suspected OSA. The control group included 42 simple snoring subjects. PSG, biochemical tests, and ultrasonographic examination were performed all subjects. RESULTS The simple snoring and mild, moderate, and severe OSA groups included 18/42 (42.86%), 33/52 (63.5%), 27/34 (79.4%), and 28/48 (79.2%) subjects with hepatosteatosis, respectively. There were significant differences in hepatosteatosis and hepatosteatosis grade between the simple snoring and the moderate and severe OSA groups. Logistic regression analysis showed that BMI and average desaturation were independently and significantly related to hepatic steatosis. CONCLUSIONS Our study shows that BMI and the average desaturation contribute to non-alcoholic fatty liver in subjects with OSA. In this regard, sleep apnea may trigger metabolic mitochondrial energy associated processes thereby altering lipid metabolism and obesity as well.
Collapse
Affiliation(s)
- Ahmet Arısoy
- Department of Pulmonary Medicine, Yuzuncu Yıl University, Van, Turkey
| | | | - Selami Ekin
- Department of Pulmonary Medicine, Yuzuncu Yıl University, Van, Turkey
| | - Mesut Özgökçe
- Department of Radiology, Yuzuncu Yıl University, Van, Turkey
| | | | | | - Şehmus Ölmez
- Department of Gastroenterology, Yuzuncu Yıl University, Van, Turkey
| | - Mahfuz Turan
- Department of Otorhinolaryngology, Yuzuncu Yıl University, Van, Turkey
| |
Collapse
|
|
25
|
Kassim R, Harris MA, Leong GM, Heussler H. Obstructive sleep apnoea in children with obesity. J Paediatr Child Health 2016; 52:284-90. [PMID: 26748912 DOI: 10.1111/jpc.13009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2015] [Indexed: 12/12/2022]
Abstract
AIMS The aim of this study was to identify factors that predict risk of obstructive sleep apnoea (OSA) in obese children, which could aid in prioritising sleep studies. METHODS A retrospective chart review was undertaken of obese children seen in the KOALA weight management clinic and Sleep clinic. Data collected included demographics, clinical history, examination findings, biochemical markers, and polysomnogram results. RESULTS Two hundred seventy-two obese children were seen in the KOALA clinic out of which 54 (20%) were also seen in the Sleep clinic because of snoring. Thirty-two were referred by the KOALA clinic; the remaining 22 were referred by other medical practitioners prior to being seen in the KOALA clinic. Thirty-nine had polysomnograms. The time from referral to Sleep clinic ranged from 10 days to 1.5 years with 50% seen within 6 months; with similar time gap between the blood tests and time of polysomnograms. Thirty-six percent (14/39) were reported to have OSA. Six children were Aboriginal/Torres Strait Islander (ATSI) and all had OSA, which was statistically significant (P = 0.004). There was a statistically significant correlation between high-sensitivity C-reactive protein (hs-CRP) and obstructive event index (OEI) in rapid eye movement (REM) sleep. (r = 0.50, P = 0.04). Correlation between low-density lipoprotein (LDL) and OEI in REM was r = 0.36, P = 0.06, which approached significance. CONCLUSIONS Ethnicity was a significant factor with more obese ATSI children having OSA. The significant correlation between hs-CRP with OEI is consistent with findings of previous studies. Several factors (glycosylated haemoglobin, LDL) approached significance.
Collapse
Affiliation(s)
- Rubina Kassim
- General Paediatrics, Mater Children's Hospital, South Brisbane, Queensland, Australia
| | - Margaret-Anne Harris
- Department of Paediatric Respiratory and Sleep Medicine, Mater Children's Hospital, South Brisbane, Queensland, Australia
| | - Gary M Leong
- Department of Paediatric Endocrinology and Diabetes, Mater Children's Hospital, South Brisbane, Queensland, Australia
| | - Helen Heussler
- Department of Paediatric Respiratory and Sleep Medicine, Mater Children's Hospital, South Brisbane, Queensland, Australia
| |
Collapse
|
|
26
|
Abstract
Obstructive sleep apnoea (OSA) is one of the most common causes of sleep-disordered breathing (SDB) in children. It is associated with significant morbidity, potentially impacting on long-term neurocognitive and behavioural development, as well as cardiovascular outcomes and metabolic homeostasis. The low grade systemic inflammation and increased oxidative stress seen in this condition are believed to underpin the development of these OSA-related morbidities. The significant variance in degree of end organ morbidity in patients with the same severity of OSA highlights the importance of the interplay of genetic and environmental factors in determining the overall OSA phenotype. This review seeks to summarize the current understanding of the aetiology and mechanisms underlying OSA, its risk factors, diagnosis and treatment.
Collapse
Affiliation(s)
- Eleonora Dehlink
- 1 Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, UK ; 2 National Heart and Lung Institute, Imperial College, London, UK
| | - Hui-Leng Tan
- 1 Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, UK ; 2 National Heart and Lung Institute, Imperial College, London, UK
| |
Collapse
|
|
27
|
Li J, Zhang YL, Chen R, Wang Y, Xiong KP, Huang JY, Han F, Liu CF. Elevated Serum Liver Enzymes in Patients with Obstructive Sleep Apnea-hypopnea Syndrome. Chin Med J (Engl) 2015; 128:2983-7. [PMID: 26608975 PMCID: PMC4795259 DOI: 10.4103/0366-6999.168943] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients. METHODS All patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5-14 events/h, 15-29 events/h, and ≥30 events/h. RESULTS A total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO 2 ), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation. CONCLUSIONS Our data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS.
Collapse
Affiliation(s)
- Jie Li
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Yan-Lin Zhang
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Rui Chen
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Yi Wang
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Kang-Ping Xiong
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Jun-Ying Huang
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Fei Han
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
| | - Chun-Feng Liu
- Department of Neurology and Sleep Center, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
- Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China
- Beijing Key Laboratory for Parkinson's Disease, Beijing 100053, China
| |
Collapse
|
|
28
|
Abstract
Sleep-disordered breathing (SDB) refers to a group of disorders characterized by abnormalities of respiration or ventilation during sleep. It encompasses obstructive sleep apnea (OSA), central sleep apnea (CSA) syndromes, sleep-related hypoventilation and sleep-related hypoxemia disorders. This review will concentrate on the disorder most prevalent in pediatrics, i.e., OSA, highlighting the most recent developments in our understanding of the etiology, pathophysiology and treatment options of this condition. OSA morbidities primarily involve the neurocognitive, cardiovascular and metabolic systems. However, there can be significant phenotypic variation in terms of end organ morbidity for the same OSA severity. This is likely due to the interplay between genetic and environmental factors; recent developments in the fields of genomics and proteomics have the potential to shed light on these complex pathological cascades. As we enter the era of personalized medicine, phenotyping patients to enable clinicians to tailor bespoke clinical management plans will be of crucial importance.
Collapse
|
|
29
|
Quante M, Wang R, Weng J, Rosen CL, Amin R, Garetz SL, Katz E, Paruthi S, Arens R, Muzumdar H, Marcus CL, Ellenberg S, Redline S. The Effect of Adenotonsillectomy for Childhood Sleep Apnea on Cardiometabolic Measures. Sleep 2015; 38:1395-403. [PMID: 25669177 DOI: 10.5665/sleep.4976] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 12/08/2014] [Indexed: 02/01/2023] Open
Abstract
STUDY OBJECTIVES Obstructive sleep apnea syndrome (OSAS) has been associated with cardiometabolic disease in adults. In children, this association is unclear. We evaluated the effect of early adenotonsillectomy (eAT) for treatment of OSAS on blood pressure, heart rate, lipids, glucose, insulin, and C-reactive protein. We also analyzed whether these parameters at baseline and changes at follow-up correlated with polysomnographic indices. DESIGN Data collected at baseline and 7-mo follow-up were analyzed from a randomized controlled trial, the Childhood Adenotonsillectomy Trial (CHAT). SETTING Clinical referral setting from multiple centers. PARTICIPANTS There were 464 children, ages 5 to 9.9 y with OSAS without severe hypoxemia. INTERVENTIONS Randomization to eAT or Watchful Waiting with Supportive Care (WWSC). MEASUREMENTS AND RESULTS There was no significant change of cardiometabolic parameters over the 7-mo interval in the eAT group compared to WWSC group. However, overnight heart rate was incrementally higher in association with baseline OSAS severity (average heart rate increase of 3 beats per minute [bpm] for apnea-hypopnea index [AHI] of 2 versus 10; [standard error = 0.60]). Each 5-unit improvement in AHI and 5 mmHg improvement in peak end-tidal CO2 were estimated to reduce heart rate by 1 and 1.5 bpm, respectively. An increase in N3 sleep also was associated with small reductions in systolic blood pressure percentile. CONCLUSIONS There is little variation in standard cardiometabolic parameters in children with obstructive sleep apnea syndrome (OSAS) but without severe hypoxemia at baseline or after intervention. Of all measures, overnight heart rate emerged as the most sensitive parameter of pediatric OSAS severity. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov (#NCT00560859).
Collapse
Affiliation(s)
- Mirja Quante
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Rui Wang
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Jia Weng
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital, Boston, MA
| | - Carol L Rosen
- Department of Pediatrics, Rainbow Babies and Children's Hospital, University Hospitals-Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH
| | - Raouf Amin
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Susan L Garetz
- Department of Otolaryngology, Head and Neck Surgery and Sleep Disorders Center, University of Michigan Medical Center, Ann Arbor, MI
| | - Eliot Katz
- Harvard Medical School, Boston, MA.,Department of Pediatrics, Boston Children's Hospital, Boston, MA
| | - Shalini Paruthi
- Department of Pediatrics, Cardinal Glennon Children's Hospital, Saint Louis University, St Louis, MO
| | - Raanan Arens
- Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Hiren Muzumdar
- Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Carole L Marcus
- Sleep Center, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
| | - Susan Ellenberg
- Department of Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Susan Redline
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital, Boston, MA.,Harvard Medical School, Boston, MA.,Beth Israel Deaconess Medical Center, Boston, MA
| | | |
Collapse
|
|
30
|
Nobili V, Alisi A, Cutrera R, Carpino G, De Stefanis C, D'Oria V, De Vito R, Cucchiara S, Gaudio E, Musso G. Altered gut-liver axis and hepatic adiponectin expression in OSAS: novel mediators of liver injury in paediatric non-alcoholic fatty liver. Thorax 2015; 70:769-81. [PMID: 26069285 DOI: 10.1136/thoraxjnl-2015-206782] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 05/26/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Mechanism(s) connecting obstructive sleep apnoea syndrome (OSAS) to liver injury in paediatric non-alcoholic fatty liver disease (NAFLD) are unknown. We hypothesised alterations in gut-liver axis and in the pool and phenotype of hepatic progenitor cells (HPCs) may be involved in OSAS-associated liver injury in NAFLD. METHODS Eighty biopsy-proven NAFLD children (age, mean±SD, 11.4±2.0 years, 56% males, body mass index z-score 1.95±0.57) underwent a clinical-biochemical assessment, with measurement of insulin sensitivity, plasma cytokines, lipopolysaccharide (LPS), an intestinal permeability test and a standard polysomnography. Hepatic toll-like receptor (TLR)-4 expression by liver-resident cells and overall number and expression of resistin and adiponectin by HPCs were assessed by immunofluorescence and immunohistochemistry. OSAS was defined by an apnoea/hypopnoea index ≥1. RESULTS OSAS was characterised by an increased intestinal permeability and endotoxemia, coupled with TLR-4 upregulation in hepatocytes, Kupffer and hepatic stellate cells (HSCs) and by an expansion of an adiponectin-deficient HPC pool, key features of steatohepatitis and fibrosis.The duration of haemoglobin desaturation (SaO2 <90%) independently predicted intestinal permeability (β: 0.396; p=0.026), plasma LPS (β: 0.358; p=0.008) and TLR-4 expression by hepatocytes (β: 0.332; p=0.009), Kupffer cells (β: 0.357; p=0.006) and HSCs (β:0.445; p=0.002).SaO2 <90% predicted also HPC number (β: 0.471; p=0.001) and impaired adiponectin expression by HPC pool (β: -0.532; p=0.0009).These relationships were observed in obese and non-obese children. CONCLUSIONS In paediatric NAFLD, OSAS is associated with increased endotoxemia coupled with impaired gut barrier function, with increased TLR-4-mediated hepatic susceptibility to endotoxemia and with an expansion of an adiponectin-deficient HPC pool. These alterations may represent a novel pathogenic link and a potential therapeutic target for OSAS-associated liver injury in NAFLD.
Collapse
Affiliation(s)
- Valerio Nobili
- Hepato-Metabolic Disease Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy
| | - Anna Alisi
- Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy
| | - Renato Cutrera
- Pneumology Unit-Sleep and NIV Laboratory, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | | | - Valentina D'Oria
- Confocal Microscopy Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy
| | - Rita De Vito
- Pathology Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy
| | - Salvatore Cucchiara
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Eugenio Gaudio
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University, Rome, Italy
| | - Giovanni Musso
- Gradenigo Hospital C.so Regina Margherita 8, Turin, Italy
| |
Collapse
|
|
31
|
Hakim F, Kheirandish-Gozal L, Gozal D. Obesity and Altered Sleep: A Pathway to Metabolic Derangements in Children? Semin Pediatr Neurol 2015; 22:77-85. [PMID: 26072337 PMCID: PMC4466552 DOI: 10.1016/j.spen.2015.04.006] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Obstructive sleep apnea (OSA) is a frequent disorder in children and is primarily associated with adenotonsillar hypertrophy. The prominent increases in childhood overweight and obesity rates in the world even among youngest of children have translated into parallel increases in the prevalence of OSA, and such trends are undoubtedly associated with deleterious global health outcomes and life expectancy. Even an obesity phenotype in childhood OSA, more close to the adult type, has been recently proposed. Reciprocal interactions between sleep in general, OSA, obesity, and disruptions of metabolic homeostasis have emerged in recent years. These associations have suggested the a priori involvement of complex sets of metabolic and inflammatory pathways, all of which may underlie an increased risk for increased orexigenic behaviors and dysfunctional satiety, hyperlipidemia, and insulin resistance that ultimately favor the emergence of metabolic syndrome. Here, we review some of the critical evidence supporting the proposed associations between sleep disruption and the metabolism-obesity complex. In addition, we describe the more recent evidence linking the potential interactive roles of OSA and obesity on metabolic phenotype.
Collapse
Affiliation(s)
- Fahed Hakim
- Pediatric Pulmonary Institute, Ruth Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Leila Kheirandish-Gozal
- Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
| | - David Gozal
- Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
| |
Collapse
|
|
32
|
Effects of adenotonsillectomy on plasma inflammatory biomarkers in obese children with obstructive sleep apnea: A community-based study. Int J Obes (Lond) 2015; 39:1094-100. [PMID: 25801692 PMCID: PMC4496251 DOI: 10.1038/ijo.2015.37] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 02/23/2015] [Accepted: 03/15/2015] [Indexed: 12/30/2022]
Abstract
Background Obesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions. Aim To examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community. Methods Obese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the 2 PSG were assayed for multiple inflammatory and metabolic markers including interleukin-6 (IL-6), IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase- (MMP-9), adiponectin, apelin C, leptin and osteocrin. Results Out of 122 potential candidates, 100 obese children with OSA completed the study with only 1/3 exhibiting normalization of their PSG after T&A (i.e., AHI≤1/hrTST). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (i.e., AHI≥/hrTST). Conclusions A defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.
Collapse
|
|
33
|
da Rosa DP, Forgiarini LF, e Silva MB, Fiori CZ, Andrade CF, Martinez D, Marroni NP. Antioxidants inhibit the inflammatory and apoptotic processes in an intermittent hypoxia model of sleep apnea. Inflamm Res 2014; 64:21-9. [PMID: 25380745 DOI: 10.1007/s00011-014-0778-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 09/18/2014] [Accepted: 09/22/2014] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Sleep apnea causes intermittent hypoxia (IH). We aimed to investigate the proteins related to oxidative stress, inflammation and apoptosis in liver tissue subjected to IH as a simulation of sleep apnea in conjunction with the administration of either melatonin (MEL, 200 μL/kg) or N-acetylcysteine (NAC, 10 mg/kg). METHODS Seventy-two adult male Balb-C mice were divided: simulation of IH (SIH), SIH + MEL, SIH + NAC, IH, IH + MEL and IH + NAC. The animals were subjected to simulations of sleep apnea for 8 h a day for 35 days. The data were analyzed with ANOVA and Tukey tests with the significance set at p < 0.05. RESULTS In IH, there was a significant increase in oxidative stress and expression of HIF-1a. In addition, we observed increase in the activation levels of NF-kB. This increase may be responsible for the increased expression of TNF-alpha and iNOS as well as the significant increase of VEGF signaling and expression of caspase-3 and caspase-6, which suggests an increase in apoptosis. In the groups treated with antioxidants, the analysis showed that the enzyme activity and protein levels were similar to those of the non-simulated group. CONCLUSIONS Thus, we show that IH causes liver inflammation and apoptosis, which may be protected with either MEL or NAC.
Collapse
Affiliation(s)
- Darlan Pase da Rosa
- Programa de Pós-Graduação Medicina, Ciências Médicas, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, CEP 90670-001, Brazil,
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Suzuki T, Shinjo S, Arai T, Kanai M, Goda N. Hypoxia and fatty liver. World J Gastroenterol 2014; 20:15087-15097. [PMID: 25386057 PMCID: PMC4223242 DOI: 10.3748/wjg.v20.i41.15087] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 02/14/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.
Collapse
|
|
35
|
Mathew JL, Narang I. Sleeping too close together: obesity and obstructive sleep apnea in childhood and adolescence. Paediatr Respir Rev 2014; 15:211-8. [PMID: 24094775 DOI: 10.1016/j.prrv.2013.09.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
To review the current available literature exploring the prevalence, severity, consequences and treatments for obesity related OSA in children and adolescents. The published literature was searched through EMBASE and Pubmed using a pre-defined search strategy. There is evidence showing that OSA occurs more frequently and may be more severe in children and adolescents who are overweight or obese compared with lean children. Obesity and OSA are independently associated with adverse cardiovascular, metabolic, and neuropsychological consequences. The magnitude of these abnormalities when obesity and OSA co-exist is not well established. Treatment options for obesity related OSA includes adenotonsillectomy, but it does not cure OSA in over 50% of obese children. Positive airway pressure (PAP) therapy delivered through continuous or bi-level modes is successful, but limited by generally poor compliance. There is increasing experience with bariatric surgical techniques which are effective for the treatment of obesity and its related complications. As obesity related OSA is highly prevalent, more research is needed to understand the interaction of these two conditions with regards to pathophysiology, adverse consequences and optimal management strategies.
Collapse
Affiliation(s)
- Joseph L Mathew
- Pediatric Pulmonology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012
| | - Indra Narang
- Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Canada; The University of Toronto, Toronto, Canada.
| |
Collapse
|
|
36
|
Bhattacharjee R, Gozal D. Sleep Hypoventilation Syndromes and Noninvasive Ventilation in Children. Sleep Med Clin 2014. [DOI: 10.1016/j.jsmc.2014.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
37
|
Sookoian S, Pirola CJ. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis. Obes Surg 2014. [PMID: 23740153 DOI: 10.1007/s11695-13-0981-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis. METHODS Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD. RESULTS From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation. CONCLUSIONS Routine assessment of liver enzymes and liver damage should be implemented in OSA patients because they have an increase of 13.3% of ALT and 4.4% of AST levels, and a 2.6-fold higher risk of liver fibrosis when they have NAFLD, which is 2.6 times more frequent in OSA patients.
Collapse
Affiliation(s)
- Silvia Sookoian
- Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina,
| | | |
Collapse
|
|
38
|
Sookoian S, Pirola CJ. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis. Obes Surg 2014; 23:1815-25. [PMID: 23740153 DOI: 10.1007/s11695-013-0981-4] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis. METHODS Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD. RESULTS From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation. CONCLUSIONS Routine assessment of liver enzymes and liver damage should be implemented in OSA patients because they have an increase of 13.3% of ALT and 4.4% of AST levels, and a 2.6-fold higher risk of liver fibrosis when they have NAFLD, which is 2.6 times more frequent in OSA patients.
Collapse
Affiliation(s)
- Silvia Sookoian
- Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina,
| | | |
Collapse
|
|
39
|
Association between nocturnal hypoxia and liver injury in the setting of nonalcoholic fatty liver disease. Sleep Breath 2014; 19:273-80. [PMID: 24870112 PMCID: PMC4330463 DOI: 10.1007/s11325-014-1008-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 05/12/2014] [Accepted: 05/14/2014] [Indexed: 02/08/2023]
Abstract
Purpose Obstructive sleep apnea (OSA) is suggested as a potential risk factor of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is still far from clear. The aim of this observational study was to investigate the influence of OSA-related hypoxia on severity of liver injury in patients with NAFLD. Methods Consecutive patients with ultrasound-diagnosed NAFLD who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Subjects were divided into control, moderate, and severe groups. Results A total of 85 subjects with 73 males and 12 females were included (mean age, 44.67 ± 1.28 years; mean body mass index, 27.28 ± 0.33 kg/m2). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, gamma glutamyltransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose, and high-sensitivity C-reactive protein significantly increased with the aggravation of OSA. In multivariate analysis, oxygen desaturation index was the major contributing factor for elevated ALT (β = 0.435, p = 0.000), average O2 saturation was the major independent predictor of elevated AST (β = −0.269, p = 0.020). Conclusions OSA-related hypoxia was independently associated with the biochemical evidence of liver injury in the presence of NAFLD.
Collapse
|
|
40
|
Waist-to-height ratio distinguish obstructive sleep apnea from primary snoring in obese children. Sleep Breath 2014; 19:231-7. [DOI: 10.1007/s11325-014-1001-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2014] [Revised: 04/17/2014] [Accepted: 04/30/2014] [Indexed: 11/26/2022]
|
|
41
|
Minville C, Hilleret MN, Tamisier R, Aron-Wisnewsky J, Clement K, Trocme C, Borel JC, Lévy P, Zarski JP, Pépin JL. Nonalcoholic fatty liver disease, nocturnal hypoxia, and endothelial function in patients with sleep apnea. Chest 2014; 145:525-533. [PMID: 24264333 DOI: 10.1378/chest.13-0938] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Nocturnal hypoxia, the hallmark of OSA, is a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). NAFLD severity and its implication in OSA-related endothelial dysfunction have not been investigated in a large, unselected OSA population, including nonobese subjects. METHODS Noninvasive blood tests (SteatoTest, NashTest, and FibroTest) were used to evaluate steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis in a large cohort of patients with OSA. In the same group, endothelial function and its links with NAFLD severity were assessed. RESULTS Of the 226 subjects included who were referred for suspicion of OSA (men, 55%; median age, 56 years; median BMI, 34.2 kg/m2 [33% with BMI<30 kg/m2]), 61.5% exhibited moderate or severe steatosis. By multivariate analysis, independent factors for liver steatosis were, as expected, triglyceride levels (P<.0001) and insulin resistance (P=.0004) as well as nocturnal cumulative time spent<90% of oxygen saturation (CT90) (P=.01). Thirty-eight percent had borderline or possible NASH (N1 or N2 with NashTest). CT90 was significantly associated with borderline or possible NASH (P=.035) in univariate but not in multivariate analysis. The dose-response relationship between the severity of nocturnal hypoxia and liver injury was established only in morbid obesity and not in lean. Multivariate models showed that steatosis was independently associated with endothelial dysfunction after adjustment for confounders. CONCLUSIONS In a large, unselected OSA population, the severity of nocturnal hypoxia was independently associated with steatosis. Preexisting obesity exacerbated the effects of nocturnal hypoxemia. NAFLD is a potential mechanism of endothelial dysfunction in OSA.
Collapse
Affiliation(s)
- Caroline Minville
- Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, QC, Canada; Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France
| | | | - Renaud Tamisier
- Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France
| | - Judith Aron-Wisnewsky
- Assistance Publique-Hôpitaux de Paris, Département Cœur et métabolisme, Centre de Nutrition Humaine, Hôpital Pitié-Salpétrière, Paris 75613, France; INSERM UMRS 872 team 7, Nutriomique, Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, Paris 75006, France
| | - Karine Clement
- Assistance Publique-Hôpitaux de Paris, Département Cœur et métabolisme, Centre de Nutrition Humaine, Hôpital Pitié-Salpétrière, Paris 75613, France; INSERM UMRS 872 team 7, Nutriomique, Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, Paris 75006, France
| | - Candice Trocme
- Laboratoire de Biochimie des Enzymes et des Protéines, CGD (Institut de Biologie et de Pathologie), CHU de Grenoble, France
| | - Jean-Christian Borel
- Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France.
| | - Patrick Lévy
- Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France
| | - Jean-Pierre Zarski
- Département d'Hépato Gastroentérologie, Pôle Digidune, CHU de Grenoble, France
| | - Jean-Louis Pépin
- Université Joseph Fourier, INSERM U 1042, Laboratoire HP2, Hypoxie Physiopathologies, Pôle Locomotion, Rééducation et Physiologie, CHU de Grenoble, France
| |
Collapse
|
|
42
|
Sundaram SS, Sokol RJ, Capocelli KE, Pan Z, Sullivan JS, Robbins K, Halbower AC. Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease. J Pediatr 2014; 164:699-706.e1. [PMID: 24321532 PMCID: PMC4014349 DOI: 10.1016/j.jpeds.2013.10.072] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Revised: 09/25/2013] [Accepted: 10/24/2013] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. RESULTS Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). CONCLUSION Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity.
Collapse
Affiliation(s)
- Shikha S. Sundaram
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - Ronald J. Sokol
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | | | - Zhaoxing Pan
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO
| | - Jillian S. Sullivan
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - Kristen Robbins
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | | |
Collapse
|
|
43
|
Nobili V, Cutrera R, Liccardo D, Pavone M, Devito R, Giorgio V, Verrillo E, Baviera G, Musso G. Obstructive sleep apnea syndrome affects liver histology and inflammatory cell activation in pediatric nonalcoholic fatty liver disease, regardless of obesity/insulin resistance. Am J Respir Crit Care Med 2014; 189:66-76. [PMID: 24256086 DOI: 10.1164/rccm.201307-1339oc] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
RATIONALE Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are frequently encountered in obese children. Whether OSAS and intermittent hypoxia are associated with liver injury in pediatric NAFLD is unknown. OBJECTIVES To assess the relationship of OSAS with liver injury in pediatric NAFLD. METHODS Sixty-five consecutive children with biopsy-proven NAFLD (age, mean ± SD, 11.7 ± 2.1 yr; 58% boys; body mass index z score, 1.93 ± 0.61) underwent a clinical-biochemical assessment and a standard polysomnography. Insulin sensitivity, circulating proinflammatory cytokines, markers of hepatocyte apoptosis (cytokeratin-18 fragments), and hepatic fibrogenesis (hyaluronic acid) were measured. Liver inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3, and CD163, surface markers of leukocytes, T cells, and activated macrophage/Kupffer cells, respectively. OSAS was defined by an apnea/hypopnea index (AHI) greater than or equal to 1 event/h, and severe OSAS was defined by an AHI greater than or equal to 5 events/h. MEASUREMENTS AND MAIN RESULTS Fifty-five percent of children with NAFLD had nonalcoholic steatohepatitis (NASH), and 34% had significant (stage F ≥ 2) fibrosis. OSAS affected 60% of children with NAFLD; the presence and severity of OSAS were associated with the presence of NASH (odds ratio, 4.89; 95% confidence interval, 3.08-5.98; P = 0.0001), significant fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23-7.42; P = 0.0001), and NAFLD activity score (β, 0.347; P = 0.029), independently of body mass index, abdominal adiposity, metabolic syndrome, and insulin resistance. This relationship held also in nonobese children with NAFLD. The duration of hemoglobin desaturation (Sa(O2) < 90%) correlated with increased intrahepatic leukocytes and activated macrophages/Kupffer cells and with circulating markers of hepatocyte apoptosis and fibrogenesis. CONCLUSIONS In pediatric NAFLD, OSAS is associated with biochemical, immunohistochemical, and histological features of NASH and fibrosis. The impact of hypoxemia correction on liver disease severity warrants evaluation in future trials.
Collapse
|
|
44
|
Ogata C, Ohmoto-Sekine Y, Tanabe M, Iwao A, Hsieh SD, Amakawa K, Matsumoto N, Ogawa K, Arimoto S, Okuda C, Shiba M, Kato H, Hashimoto M, Ishihara M, Tsuji H, Hara S, Arase Y. Prognostic factors for regression from impaired glucose tolerance to normal glucose regulation in Japanese patients with nonalcoholic fatty liver disease. Intern Med 2014; 53:1401-6. [PMID: 24990331 DOI: 10.2169/internalmedicine.53.1585] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE The aim of this retrospective cohort study was to assess the predictive factors for the regression from impaired glucose tolerance (IGT) to normal glucose regulation (NGR) in patients with nonalcoholic fatty liver disease (NAFLD). METHODS A total of 164 NAFLD patients who had IGT in the first 75-g oral glucose tolerance test (OGTT) and underwent a repeated OGTT five years later were enrolled. A multivariate logistic regression analysis was carried out to identify factors predicting the regression from IGT to NGR. RESULTS Out of the 164 patients, 29 regressed from IGT to NGR within five years after the first OGTT. The multivariate analysis by logistic regression showed that regression from IGT to NGR occurred when the patient was young (risk ratio for ten years: 0.38; 95% confidence interval [CI] 0.20-0.72; p=0.003), had a fasting plasma glucose (FPG) level of <100 mg/dL (risk ratio: 6.53; 95%CI 1.88-21.73; p=0.003), had a 2-hr post-load plasma glucose (PG) level of <160 mg/dL (risk ratio: 4.86; 95%CI 1.08-22.72; p=0.040), a body mass index (BMI) decrease of ≥1.5 (risk ratio: 5.20; 95% CI 1.41-19.24; p=0.014), physical activity of ≥2 Metabolic Equivalent of Task (MET) h/day (risk ratio: 5.57; 95%CI 1.68-18.44; p=0.005), and showed disappearance of the fatty liver by ultrasonography at five years (risk ratio: 9.92; 95%CI 2.87-34.34; p<0.001). CONCLUSION Our results suggest that six factors: young age, FPG <100 mg/dL, 2-hr post-load PG of <160 mg/dL, BMI decrease of ≥1.5, physical activity of ≥2 MET h/day, and the disappearance of fatty liver predict the regression from IGT to NGR in NAFLD patients.
Collapse
Affiliation(s)
- Chie Ogata
- Department of Health Management Center, Toranomon Hospital, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Van Hoorenbeeck K, Verhulst SL. Metabolic complications and obstructive sleep apnea in obese children: time to wake up! Am J Respir Crit Care Med 2014; 189:13-5. [PMID: 24381991 DOI: 10.1164/rccm.201311-2079ed] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
|
46
|
Arase Y, Kawamura Y, Seko Y, Kobayashi M, Suzuki F, Suzuki Y, Akuta N, Kobayashi M, Sezaki H, Saito S, Hosaka T, Ikeda K, Kumada H, Ohmoto-Sekine Y, Hsieh SD, Amakawa K, Ogawa K, Matsumoto N, Iwao A, Tsuji H, Hara S, Mori Y, Okubo M, Sone H, Kobayashi T. Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease. Hepatol Res 2013; 43:1163-8. [PMID: 23489256 DOI: 10.1111/hepr.12077] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2012] [Revised: 12/25/2012] [Accepted: 01/20/2013] [Indexed: 12/12/2022]
Abstract
AIM The aim of this case-control study was to assess the efficacy and safety of dipeptidyl peptidase-4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD). METHODS Twenty NAFLD patients with T2DM treated by sitagliptin were retrospectively enrolled as the sitagliptin group. These patients were given sitagliptin between January 2010 and July 2011. Another 20 NAFLD patients with T2DM treated only with diet and exercise for 48 weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48 weeks after the initiation of treatment. RESULTS In the sitagliptin group, average HbA1c levels decreased approximately 0.7% at 48 weeks after the initiation of sitagliptin. Next, average FPG levels decreased approximately 15 mg/dL at 48 weeks after the initiation of sitagliptin. The serum levels of HbA1c and FPG in the sitagliptin group decreased with statistical significance compared to those in the control group (P < 0.05). All the patients could take sitagliptin of 50 mg/day without reduction necessitated by sitagliptin-related side-effects. There were no significant changes of average AST and ALT levels during follow up of 48 weeks in both sitagliptin and control groups. CONCLUSION Our results indicate sitagliptin is effective and safe for the treatment of T2DM complicated with NAFLD.
Collapse
Affiliation(s)
- Yasuji Arase
- Department of Hepatology and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Department of Health Management Center, Toranomon Hospital, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Abstract
Obstructive sleep apnea (OSA) in children is a highly prevalent disorder caused by a conglomeration of complex pathophysiological processes, leading to recurrent upper airway dysfunction during sleep. The clinical relevance of OSA resides in its association with significant morbidities that affect the cardiovascular, neurocognitive, and metabolic systems. The American Academy of Pediatrics recently reiterated its recommendations that children with symptoms and signs suggestive of OSA should be investigated with polysomnography (PSG), and treated accordingly. However, treatment decisions should not only be guided by PSG results, but should also integrate the magnitude of symptoms and the presence or absence of risk factors and signs of OSA morbidity. The first-line therapy in children with adenotonsillar hypertrophy is adenotonsillectomy, although there is increasing evidence that medical therapy, in the form of intranasal steroids or montelukast, may be considered in mild OSA. In this review, we delineate the major concepts regarding the pathophysiology of OSA, its morbidity, diagnosis, and treatment.
Collapse
Affiliation(s)
- Hui-Leng Tan
- Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Comer Children’s Hospital, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA
- Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
| | - David Gozal
- Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Comer Children’s Hospital, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA
| | - Leila Kheirandish-Gozal
- Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Comer Children’s Hospital, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA
| |
Collapse
|
|
48
|
Van Hoorenbeeck K, Franckx H, Debode P, Aerts P, Ramet J, Van Gaal LF, Desager KN, De Backer WA, Verhulst SL. Metabolic disregulation in obese adolescents with sleep-disordered breathing before and after weight loss. Obesity (Silver Spring) 2013; 21:1446-50. [PMID: 23408643 DOI: 10.1002/oby.20337] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2012] [Accepted: 12/10/2012] [Indexed: 11/10/2022]
Abstract
OBJECTIVE Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. DESIGN AND METHODS Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. RESULTS 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation (<SaO2>) (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and <SaO2> (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score. CONCLUSION SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements.
Collapse
Affiliation(s)
- K Van Hoorenbeeck
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Vajro P, Maddaluno S, Veropalumbo C. Persistent hypertransaminasemia in asymptomatic children: A stepwise approach. World J Gastroenterol 2013; 19:2740-2751. [PMID: 23687411 PMCID: PMC3653148 DOI: 10.3748/wjg.v19.i18.2740] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Revised: 12/20/2012] [Accepted: 01/19/2013] [Indexed: 02/06/2023] Open
Abstract
We aimed to examine the major causes of isolated chronic hypertransaminasemia in asymptomatic children and develop a comprehensive diagnostic flow diagram. A MEDLINE search inclusive of publications throughout August 2012 was performed. We found only a small number of publications that had comprehensively investigated this topic. Consequently, it was difficult to construct a diagnostic flowchart similar to those already available for adults. In children, a “retesting panel” prescription, including gamma-glutamyl transpeptidase and creatine kinase in addition to aminotransferases, is considered a reasonable approach for proficiently confirming the persistence of the abnormality, ruling out cholestatic hepatopathies and myopathies, and guiding the subsequent diagnostic steps. If re-evaluation of physical and historical findings suggests specific etiologies, then these should be evaluated in the initial enzyme retesting panel. A simple multi-step diagnostic algorithm incorporating a large number of possible pediatric scenarios, in addition to the few common to adults, is available. Accurately classifying a child with asymptomatic persistent hypertransaminasemia may be a difficult task, but the results are critical for preventing the progression of an underlying, possibly occult, condition later in childhood or during transition. Given the high benefit/cost ratio of preventing hepatic deterioration, no effort should be spared in diagnosing and properly treating each case of persistent hypertransaminasemia in pediatric patients.
Collapse
|
|
50
|
Zong J, Liu Y, Huang Y, Chen J, Gao L, Zhang C, Dong S, Chen X. Serum lipids alterations in adenoid hypertrophy or adenotonsillar hypertrophy children with sleep disordered breathing. Int J Pediatr Otorhinolaryngol 2013; 77:717-20. [PMID: 23434201 DOI: 10.1016/j.ijporl.2013.01.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2012] [Revised: 01/20/2013] [Accepted: 01/26/2013] [Indexed: 10/27/2022]
Abstract
OBJECTIVES We aimed to investigate metabolic parameters in children with adenoid hypertrophy (AH) only or adenotonsillar hypertrophy (ATH) and compare them with healthy controls. METHODS Forty-four prepubertal children aged 6-12 years who were obstructive symptoms and 16 healthy children were recruited in this study. All children underwent a complete otolaryngologic examination and sleep screening. The patients were divided into three groups according to obstruction type: normal, AH (adenoid grade III or IV, tonsil grade 1 or 2), and ATH (adenoid grade III or IV, tonsil grade 3 or 4). All participants underwent hematologic and biochemical tests including fasting blood glucose, insulin, and plasma lipids. RESULTS (1) The children with AH and ATH had lower high-density lipoprotein cholesterol (HDL-C), when compared to normal children. (2) The level of HDL-C was negatively correlated with the sum of adenoid and tonsillar size scores and the apnea-hypopnea index (AHI) (r=-0.477, p<0.001 vs. r=-0.548, p<0.001, respectively). There was a modest association between HDL-C and minimal SpO₂ (r=0.332, p=0.009). (3) Stepwise multiple regression analysis identified the AHI, triglycerides, and fasting insulin as independent predictors for HDL-C. CONCLUSIONS Patients with adenoid and tonsil hypertrophy had low HDL-C. HDL-C levels are inversely related to the sum of adenoid and tonsillar size scores and AHI in SDB children. HDL-C may be a sensitive indicator of serum lipids changes in SDB children.
Collapse
Affiliation(s)
- Jing Zong
- Department of Endocrinology, The Affiliated Hospital of Jiangsu University, China
| | | | | | | | | | | | | | | |
Collapse
|