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Sleep Apnea Syndromes: HELP
Articles by David Gozal
Based on 230 articles published since 2008
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Between 2008 and 2019, D. Gozal wrote the following 230 articles about Sleep Apnea Syndromes.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Guideline An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults. 2013

Schwab, Richard J / Badr, Safwan M / Epstein, Lawrence J / Gay, Peter C / Gozal, David / Kohler, Malcolm / Lévy, Patrick / Malhotra, Atul / Phillips, Barbara A / Rosen, Ilene M / Strohl, Kingman P / Strollo, Patrick J / Weaver, Edward M / Weaver, Terri E / Anonymous2650768. · ·Am J Respir Crit Care Med · Pubmed #23992588.

ABSTRACT: BACKGROUND: Continuous positive airway pressure (CPAP) is considered the treatment of choice for obstructive sleep apnea (OSA), and studies have shown that there is a correlation between patient adherence and treatment outcomes. Newer CPAP machines can track adherence, hours of use, mask leak, and residual apnea-hypopnea index (AHI). Such data provide a strong platform to examine OSA outcomes in a chronic disease management model. However, there are no standards for capturing CPAP adherence data, scoring flow signals, or measuring mask leak, or for how clinicians should use these data. METHODS: American Thoracic Society (ATS) committee members were invited, based on their expertise in OSA and CPAP monitoring. Their conclusions were based on both empirical evidence identified by a comprehensive literature review and clinical experience. RESULTS: CPAP usage can be reliably determined from CPAP tracking systems, but the residual events (apnea/hypopnea) and leak data are not as easy to interpret as CPAP usage and the definitions of these parameters differ among CPAP manufacturers. Nonetheless, ends of the spectrum (very high or low values for residual events or mask leak) appear to be clinically meaningful. CONCLUSIONS: Providers need to understand how to interpret CPAP adherence tracking data. CPAP tracking systems are able to reliably track CPAP adherence. Nomenclature on the CPAP adherence tracking reports needs to be standardized between manufacturers and AHIFlow should be used to describe residual events. Studies should be performed examining the usefulness of the CPAP tracking systems and how these systems affect OSA outcomes.

2 Guideline Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. 2012

Berry, Richard B / Budhiraja, Rohit / Gottlieb, Daniel J / Gozal, David / Iber, Conrad / Kapur, Vishesh K / Marcus, Carole L / Mehra, Reena / Parthasarathy, Sairam / Quan, Stuart F / Redline, Susan / Strohl, Kingman P / Davidson Ward, Sally L / Tangredi, Michelle M / Anonymous3090739. ·University of Florida Health Science Center, Gainesville, FL 32610, USA. richard.berry@medicine.ufl.edu ·J Clin Sleep Med · Pubmed #23066376.

ABSTRACT: The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions.The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO(2) signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults.The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for ≥ 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ 10 seconds in association with either ≥ 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is ≥ 20 seconds in duration, (2) the event is associated with an arousal or ≥ 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ the duration of 2 breaths in association with either ≥ 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO(2) are the end-tidal PCO(2) or transcutaneous PCO(2) (diagnostic study) or transcutaneous PCO(2) (titration study). For adults, sleep hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 55 mm Hg for ≥ 10 minutes or there is an increase in the arterial PCO(2) (or surrogate) ≥ 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of ≥ 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring.

3 Guideline Diagnosis and management of childhood obstructive sleep apnea syndrome. 2012

Marcus, Carole L / Brooks, Lee Jay / Draper, Kari A / Gozal, David / Halbower, Ann Carol / Jones, Jacqueline / Schechter, Michael S / Sheldon, Stephen Howard / Spruyt, Karen / Ward, Sally Davidson / Lehmann, Christopher / Shiffman, Richard N / Anonymous1960735. · ·Pediatrics · Pubmed #22926173.

ABSTRACT: OBJECTIVES: This revised clinical practice guideline, intended for use by primary care clinicians, provides recommendations for the diagnosis and management of the obstructive sleep apnea syndrome (OSAS) in children and adolescents. This practice guideline focuses on uncomplicated childhood OSAS, that is, OSAS associated with adenotonsillar hypertrophy and/or obesity in an otherwise healthy child who is being treated in the primary care setting. METHODS: Of 3166 articles from 1999-2010, 350 provided relevant data. Most articles were level II-IV. The resulting evidence report was used to formulate recommendations. RESULTS AND CONCLUSIONS: The following recommendations are made. (1) All children/adolescents should be screened for snoring. (2) Polysomnography should be performed in children/adolescents with snoring and symptoms/signs of OSAS; if polysomnography is not available, then alternative diagnostic tests or referral to a specialist for more extensive evaluation may be considered. (3) Adenotonsillectomy is recommended as the first-line treatment of patients with adenotonsillar hypertrophy. (4) High-risk patients should be monitored as inpatients postoperatively. (5) Patients should be reevaluated postoperatively to determine whether further treatment is required. Objective testing should be performed in patients who are high risk or have persistent symptoms/signs of OSAS after therapy. (6) Continuous positive airway pressure is recommended as treatment if adenotonsillectomy is not performed or if OSAS persists postoperatively. (7) Weight loss is recommended in addition to other therapy in patients who are overweight or obese. (8) Intranasal corticosteroids are an option for children with mild OSAS in whom adenotonsillectomy is contraindicated or for mild postoperative OSAS.

4 Guideline [Consensus document on sleep apnea-hypopnea syndrome in children (full version). Sociedad Española de Sueño. El Área de Sueño de la Sociedad Española de Neumología y Cirugía Torácica(SEPAR)]. 2011

Luz Alonso-Álvarez, María / Canet, Teresa / Cubell-Alarco, Magdalena / Estivill, Eduard / Fernández-Julián, Enrique / Gozal, David / Jurado-Luque, María José / Lluch-Roselló, María Amalia / Martínez-Pérez, Francisco / Merino-Andreu, Milagros / Pin-Arboledas, Gonzalo / Roure, Nuria / Sanmartí, Francesc X / Sans-Capdevila, Oscar / Segarra-Isern, Francisco / Tomás-Vila, Miguel / Terán-Santos, Joaquín / Anonymous5950728 / Anonymous5960728. ·Unidad Multidisciplinar de Sueño, CIBERES, Complejo Asistencial Universitario de Burgos, Burgos, España. ·Arch Bronconeumol · Pubmed #22682520.

ABSTRACT: -- No abstract --

5 Guideline Best clinical practices for the sleep center adjustment of noninvasive positive pressure ventilation (NPPV) in stable chronic alveolar hypoventilation syndromes. 2010

Berry, Richard B / Chediak, Alejandro / Brown, Lee K / Finder, Jonathan / Gozal, David / Iber, Conrad / Kushida, Clete A / Morgenthaler, Timothy / Rowley, James A / Davidson-Ward, Sally L / Anonymous2840675. ·Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL 32610-0225, USA. ·J Clin Sleep Med · Pubmed #20957853.

ABSTRACT: Noninvasive positive pressure ventilation (NPPV) devices are used during sleep to treat patients with diurnal chronic alveolar hypoventilation (CAH). Bilevel positive airway pressure (BPAP) using a mask interface is the most commonly used method to provide ventilatory support in these patients. BPAP devices deliver separately adjustable inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP). The IPAP and EPAP levels are adjusted to maintain upper airway patency, and the pressure support (PS = IPAP-EPAP) augments ventilation. NPPV devices can be used in the spontaneous mode (the patient cycles the device from EPAP to IPAP), the spontaneous timed (ST) mode (a backup rate is available to deliver IPAP for the set inspiratory time if the patient does not trigger an IPAP/EPAP cycle within a set time window), and the timed (T) mode (inspiratory time and respiratory rate are fxed). During NPPV titration with polysomnography (PSG), the pressure settings, backup rate, and inspiratory time (if applicable) are adjusted to maintain upper airway patency and support ventilation. However, there are no widely available guidelines for the titration of NPPV in the sleep center. A NPPV Titration Task Force of the American Academy of Sleep Medicine reviewed the available literature and developed recommendations based on consensus and published evidence when available. The major recommendations derived by this consensus process are as follows: General Recommendations: 1. The indications, goals of treatment, and side effects of NPPV treatment should be discussed in detail with the patient prior to the NPPV titration study. 2. Careful mask fitting and a period of acclimatization to low pressure prior to the titration should be included as part of the NPPV protocol. 3. NPPV titration with PSG is the recommended method to determine an effective level of nocturnal ventilatory support in patients with CAH. In circumstances in which NPPV treatment is initiated and adjusted empirically in the outpatient setting based on clinical judgment, a PSG should be utilized if possible to confirm that the final NPPV settings are effective or to make adjustments as necessary. 4. NPPV treatment goals should be individualized but typically include prevention of worsening of hypoventilation during sleep, improvement in sleep quality, relief of nocturnal dyspnea, and providing respiratory muscle rest. 5. When OSA coexists with CAH, pressure settings for treatment of OSA may be determined during attended NPPV titration PSG following AASM Clinical Guidelines for the Manual Titration of Positive Airway Pressure in Patients with Obstructive Sleep Apnea. 6. Attended NPPV titration with PSG is the recommended method to identify optimal treatment pressure settings for patients with the obesity hypoventilation syndrome (OHS), CAH due to restrictive chest wall disease (RTCD), and acquired or central CAH syndromes in whom NPPV treatment is indicated. 7. Attended NPPV titration with PSG allows definitive identification of an adequate level of ventilatory support for patients with neuromuscular disease (NMD) in whom NPPV treatment is planned. Recommendations for NPPV Titration Equipment: 1. The NPPV device used for titration should have the capability of operating in the spontaneous, spontaneous timed, and timed mode. 2. The airflow, tidal volume, leak, and delivered pressure signals from the NPPV device should be monitored and recorded if possible. The airflow signal should be used to detect apnea and hypopnea, while the tidal volume signal and respiratory rate are used to assess ventilation. 3. Transcutaneous or end-tidal PCO2 may be used to adjust NPPV settings if adequately calibrated and ideally validated with arterial blood gas testing. 4. An adequate assortment of masks (nasal, oral, and oronasal) in both adult and pediatric sizes (if children are being titrated), a source of supplemental oxygen, and heated humidification should be available. Recommendations for Limits of IPAP, EPAP, and PS Settings: 1. The recommended minimum starting IPAP and EPAP should be 8 cm H2O and 4 cm H2O, respectively. 2. The recommended maximum IPAP should be 30 cm H2O for patients > or = 12 years and 20 cm H2O for patients < 12 years. 3. The recommended minimum and maximum levels of PS are 4 cm H2O and 20 cm H2O, respectively. 4. The minimum and maximum incremental changes in PS should be 1 and 2 cm H2O, respectively. Recommendations for Adjustment of IPAP, EPAP, and PS: 1. IPAP and/or EPAP should be increased as described in AASM Clinical Guidelines for the Manual Titration of Positive Airway Pressure in Patients with Obstructive Sleep Apnea until the following obstructive respiratory events are eliminated (no specific order): apneas, hypopneas, respiratory effort-related arousals, and snoring. 2. The pressure support (PS) should be increased every 5 minutes if the tidal volume is low (< 6 to 8 mL/kg) 3. The PS should be increased if the arterial PCO2 remains 10 mm Hg or more above the PCO, goal at the current settings for 10 minutes or more. An acceptable goal for PCO, is a value less than or equal to the awake PCO2. 4. The PS may be increased if respiratory muscle rest has not been achieved by NPPV treatment at the current settings for 10 minutes of more. 5. The PS may be increased if the SpO, remains below 90% for 5 minutes or more and tidal volume is low (< 6 to 8 mL/kg). Recommendations for Use and Adjustment of the Backup Rate/ Respiratory Rate: 1. A backup rate (i.e., ST mode) should be used in all patients with central hypoventilation, those with a significant number of central apneas or an inappropriately low respiratory rate, and those who unreliably trigger IPAP/EPAP cycles due to muscle weakness. 2. The ST mode may be used if adequate ventilation or adequate respiratory muscle rest is not achieved with the maximum (or maximum tolerated) PS in the spontaneous mode. 3. The starting backup rate should be equal to or slightly less than the spontaneous sleeping respiratory rate (minimum of 10 bpm). 4. The backup rate should be increased in 1 to 2 bpm increments every 10 minutes if the desired goal of the backup rate has not been attained. 5. The IPAP time (inspiratory time) should be set based on the respiratory rate to provide an inspiratory time (IPAP time) between 30% and 40% of the cycle time (60/respiratory rate in breaths per minute). 6. If the spontaneous timed mode is not successful at meeting titration goals then the timed mode can be tried. Recommendations Concerning Supplemental Oxygen: 1. Supplemental oxygen may be added in patients with an awake SpO2 < 88% or when the PS and respiratory rate have been optimized but the SpO2 remains < 90% for 5 minutes or more. 2. The minimum starting supplemental oxygen rate should be 1 L/minute and increased in increments of 1 L/minute about every 5 minutes until an adequate SpO2 is attained (> 90%). Recommendations to Improve Patient Comfort and Patient-NPPV Device Synchrony: 1. If the patient awakens and complains that the IPAP and/or EPAP is too high, pressure should be lowered to a level comfortable enough to allow return to sleep. 2. NPPV device parameters (when available) such as pressure relief, rise time, maximum and minimum IPAP durations should be adjusted for patient comfort and to optimize synchrony between the patient and the NPPV device. 3. During the NPPV titration mask refit, adjustment, or change in mask type should be performed whenever any significant unintentional leak is observed or the patient complains of mask discomfort. If mouth leak is present and is causing significant symptoms (e.g., arousals) use of an oronasal mask or chin strap may be tried. Heated humidification should be added if the patient complains of dryness or significant nasal congestion. Recommendations for Follow-Up: 1. Close follow-up after initiation of NPPV by appropriately trained health care providers is indicated to establish effective utilization patterns, remediate side effects, and assess measures of ventilation and oxygenation to determine if adjustment to NPPV is indicated.

6 Guideline Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. 2008

Kushida, Clete A / Chediak, Alejandro / Berry, Richard B / Brown, Lee K / Gozal, David / Iber, Conrad / Parthasarathy, Sairam / Quan, Stuart F / Rowley, James A / Anonymous6390598 / Anonymous6400598. ·Stanford University Center of Excellence for Sleep Disorders, 401 Quarry Road, Suite 3301, Stanford, CA 94305-5730, USA. ·J Clin Sleep Med · Pubmed #18468315.

ABSTRACT: Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBDs), including obstructive sleep apnea (OSA). After a patient is diagnosed with OSA, the current standard of practice involves performing attended polysomnography (PSG), during which positive airway pressure is adjusted throughout the recording period to determine the optimal pressure for maintaining upper airway patency. Continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP) represent the two forms of PAP that are manually titrated during PSG to determine the single fixed pressure of CPAP or the fixed inspiratory and expiratory positive airway pressures (IPAP and EPAP, respectively) of BPAP for subsequent nightly usage. A PAP Titration Task Force of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Task Force developed these recommendations for conducting CPAP and BPAP titrations. Major recommendations are as follows: (1) All potential PAP titration candidates should receive adequate PAP education, hands-on demonstration, careful mask fitting, and acclimatization prior to titration. (2) CPAP (IPAP and/or EPAP for patients on BPAP) should be increased until the following obstructive respiratory events are eliminated (no specific order) or the recommended maximum CPAP (IPAP for patients on BPAP) is reached: apneas, hypopneas, respiratory effort-related arousals (RERAs), and snoring. (3) The recommended minimum starting CPAP should be 4 cm H2O for pediatric and adult patients, and the recommended minimum starting IPAP and EPAP should be 8 cm H2O and 4 cm H2O, respectively, for pediatric and adult patients on BPAP. (4) The recommended maximum CPAP should be 15 cm H2O (or recommended maximum IPAP of 20 cm H2O if on BPAP) for patients < 12 years, and 20 cm H2O (or recommended maximum IPAP of 30 cm H2O if on BPAP) for patients > or = 12 years. (5) The recommended minimum IPAP-EPAP differential is 4 cm H2O and the recommended maximum IPAP-EPAP differential is 10 cm H2O (6) CPAP (IPAP and/or EPAP for patients on BPAP depending on the type of event) should be increased by at least 1 cm H2O with an interval no shorter than 5 min, with the goal of eliminating obstructive respiratory events. (7) CPAP (IPAP and EPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 1 obstructive apnea is observed for patients < 12 years, or if at least 2 obstructive apneas are observed for patients > or = 12 years. (8) CPAP (IPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 1 hypopnea is observed for patients < 12 years, or if at least 3 hypopneas are observed for patients > or = 12 years. (9) CPAP (IPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 3 RERAs are observed for patients < 12 years, or if at least 5 RERAs are observed for patients > or = 12 years. (10) CPAP (IPAP for patients on BPAP) may be increased from any CPAP (or IPAP) level if at least 1 min of loud or unambiguous snoring is observed for patients < 12 years, or if at least 3 min of loud or unambiguous snoring are observed for patients > or = 12 years. (11) The titration algorithm for split-night CPAP or BPAP titration studies should be identical to that of full-night CPAP or BPAP titration studies, respectively. (12) If the patient is uncomfortable or intolerant of high pressures on CPAP, the patient may be tried on BPAP. If there are continued obstructive respiratory events at 15 cm H2O of CPAP during the titration study, the patient may be switched to BPAP. (13) The pressure of CPAP or BPAP selected for patient use following the titration study should reflect control of the patient's obstructive respiration by a low (preferably < 5 per hour) respiratory disturbance index (RDI) at the selected pressure, a minimum sea level SpO2 above 90% at the pressure, and with a leak within acceptable parameters at the pressure.) (14) An optimal titration reduces RDI < 5 for at least a 15-min duration and should include supine REM sleep at the selected pressure that is not continually interrupted by spontaneous arousals or awakenings. (15) A good titration reduces RDI < or = 10 or by 50% if the baseline RDI < 15 and should include supine REM sleep that is not continually interrupted by spontaneous arousals or awakenings at the selected pressure. (16) An adequate titration does not reduce the RDI < or = 10 but reduces the RDI by 75% from baseline (especially in severe OSA patients), or one in which the titration grading criteria for optimal or good are met with the exception that supine REM sleep did not occur at the selected pressure. (17) An unacceptable titration is one that does not meet any one of the above grades. (18) A repeat PAP titration study should be considered if the initial titration does not achieve a grade of optimal or good and, if it is a split-night PSG study, it fails to meet AASM criteria (i.e., titration duration should be > 3 hr).

7 Editorial The ageing brain in sleep apnoea: paradoxical resilience, survival of the fittest, or simply comparing apples and oranges? 2018

Gozal, David. ·Dept of Pediatrics, Section of Sleep Medicine, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA dgozal@uchicago.edu. ·Eur Respir J · Pubmed #29903830.

ABSTRACT: -- No abstract --

8 Editorial Pro: continuous positive airway pressure and cardiovascular prevention. 2018

Martinez-Garcia, Miguel Angel / Campos-Rodriguez, Francisco / Javaheri, Shahrokh / Gozal, David. ·Pulmonary Dept, Polytechnic and University La Fe Hospital, Valencia, Spain. · Respiratory Dept, Valme University Hospital, Seville, Spain. · Pulmonary and Sleep Division, Bethesda North Hospital, Cincinnati, OH, USA. · Dept of Pediatrics, University of Chicago, Chicago, IL, USA. ·Eur Respir J · Pubmed #29748245.

ABSTRACT: -- No abstract --

9 Editorial What Is the Future of Sleep Medicine in the United States? 2015

Phillips, Barbara / Gozal, David / Malhotra, Atul. ·1 Division of Pulmonary, Critical Care, and Sleep Medicine University of Kentucky College of Medicine Lexington, Kentucky. · 2 University of Chicago Medicine and Biological Sciences Chicago, Illinois. · 3 Pulmonary, Critical Care, and Sleep Medicine Division University of California, San Diego La Jolla, California. ·Am J Respir Crit Care Med · Pubmed #26308722.

ABSTRACT: -- No abstract --

10 Editorial Inflammation in sleep debt and sleep disorders. 2015

Kheirandish-Gozal, Leila / Gozal, David / Pépin, Jean-Louis. ·Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA. · INSERM U 1042, HP2 Laboratory, Faculté de Médecine, Université Grenoble Alpes, 38042 Grenoble, France ; CHU and Hôpital A. Michallon, Pôle Thorax et Vaisseaux, 38043 Grenoble, France. ·Mediators Inflamm · Pubmed #25883415.

ABSTRACT: -- No abstract --

11 Editorial Obesity, asthma, and sleep-disordered breathing. 2012

Kheirandish-Gozal, Leila / Gozal, David. · ·J Pediatr · Pubmed #22197465.

ABSTRACT: -- No abstract --

12 Editorial In the fight against advanced glycation end-products (AGEs), you should treat OSA, shouldn't you? 2012

Mokhlesi, Babak / Gozal, David. · ·Sleep Med · Pubmed #22137112.

ABSTRACT: -- No abstract --

13 Editorial Pediatric sleep apnea: the brain-heart connection. 2011

Bhattacharjee, Rakesh / Gozal, David. ·Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, IL. · Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, IL. Electronic address: dgozal@uchicago.edu. ·Chest · Pubmed #21540212.

ABSTRACT: -- No abstract --

14 Editorial Matters of the heart: the brain in pediatric sleep apnea. 2008

Gozal, David. · ·Am J Respir Crit Care Med · Pubmed #18832555.

ABSTRACT: -- No abstract --

15 Editorial Mr. Pickwick and his child went on a field trip and returned almost empty handed...What we do not know and imperatively need to learn about obesity and breathing during sleep in children! 2008

Spruyt, Karen / Gozal, David. · ·Sleep Med Rev · Pubmed #18790409.

ABSTRACT: -- No abstract --

16 Review Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines. 2019

Kheirandish-Gozal, Leila / Gozal, David. ·Child Health Research Institute, Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA. gozall@health.missouri.edu. · Child Health Research Institute, Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA. gozald@health.missouri.edu. ·Int J Mol Sci · Pubmed #30678164.

ABSTRACT: Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.

17 Review Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction. 2018

Khalyfa, Abdelnaby / Kheirandish-Gozal, Leila / Gozal, David. ·Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA. akhalyfa@uchicago.edu. · Department of Child Health and the Child Health Research Institute, University of Missouri School of Medicine, Columbia, MO 65201, USA. gozall@health.missouri.edu. · Department of Child Health and the Child Health Research Institute, University of Missouri School of Medicine, Columbia, MO 65201, USA. gozald@health.missouri.edu. ·Int J Mol Sci · Pubmed #30380647.

ABSTRACT: Obstructive sleep apnea (OSA) is a highly prevalent worldwide public health problem that is characterized by repetitive upper airway collapse leading to intermittent hypoxia, pronounced negative intrathoracic pressures, and recurrent arousals resulting in sleep fragmentation. Obesity is a major risk factor of OSA and both of these two closely intertwined conditions result in increased sympathetic activity, oxidative stress, and chronic low-grade inflammation, which ultimately contribute, among other morbidities, to metabolic dysfunction, as reflected by visceral white adipose tissue (VWAT) insulin resistance (IR). Circulating extracellular vesicles (EVs), including exosomes, are released by most cell types and their cargos vary greatly and reflect underlying changes in cellular homeostasis. Thus, exosomes can provide insights into how cells and systems cope with physiological perturbations by virtue of the identity and abundance of miRNAs, mRNAs, proteins, and lipids that are packaged in the EVs cargo, and are secreted from the cells into bodily fluids under normal as well as diseased states. Accordingly, exosomes represent a novel pathway via which a cohort of biomolecules can travel long distances and result in the modulation of gene expression in selected and targeted recipient cells. For example, exosomes secreted from macrophages play a critical role in innate immunity and also initiate the adaptive immune response within specific metabolic tissues such as VWAT. Under normal conditions, phagocyte-derived exosomes represent a large portion of circulating EVs in blood, and carry a protective signature against IR that is altered when secreting cells are exposed to altered physiological conditions such as those elicited by OSA, leading to emergence of IR within VWAT compartment. Consequently, increased understanding of exosome biogenesis and biology should lead to development of new diagnostic biomarker assays and personalized therapeutic approaches. Here, the evidence on the major biological functions of macrophages and exosomes as pathophysiological effectors of OSA-induced metabolic dysfunction is discussed.

18 Review Murine models of sleep apnea: functional implications of altered macrophage polarity and epigenetic modifications in adipose and vascular tissues. 2018

Trzepizur, Wojciech / Cortese, Rene / Gozal, David. ·Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, United States; Département de Pneumologie, Centre de Recherche Clinique, CHU d'Angers, Université Bretagne Loire, UNIV Angers, INSERM UMR 1063, Angers, France. · Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, United States. · Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, United States. Electronic address: dgozal@uchicago.edu. ·Metabolism · Pubmed #29154950.

ABSTRACT: Obstructive sleep apnea (OSA) is a highly prevalent disease across the lifespan, is characterized by chronic intermittent hypoxia and sleep fragmentation, and has been independently associated with substantial cardiometabolic morbidity. However, the reversibility of end-organ morbidity with treatment is not always apparent, suggesting that both tissue remodeling and epigenetic mechanisms may be operationally involved. Here, we review the cumulative evidence focused around murine models of OSA to illustrate the temporal dependencies of cardiometabolic dysfunction and its reversibility, and more particularly to discuss the critical contributions of tissue macrophages to adipose tissue insulin resistance and vascular atherogenesis. In addition, we describe initial findings potentially implicating epigenetic alterations in both the emergence of the cardiometabolic morbidity of OSA, and in its reversibility with treatment. We anticipate that improved understanding of macrophage biology and epigenetics in the context of intermittent hypoxia and sleep fragmentation will lead to discovery of novel therapeutic targets and improved cardiovascular and metabolic outcomes in OSA.

19 Review Intermittent hypoxia and cancer: Undesirable bed partners? 2018

Almendros, Isaac / Gozal, David. ·Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, 28029 Madrid, Spain. Electronic address: isaac.almendros@ub.edu. · Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, United States. ·Respir Physiol Neurobiol · Pubmed #28818483.

ABSTRACT: The deleterious effects of intermittent hypoxia (IH) on cancer biology have been primarily evaluated in the context of the aberrant circulation observed in solid tumors which results in recurrent intra-tumoral episodic hypoxia. From those studies, IH has been linked to an accelerated tumor progression, metastasis and resistance to therapies. More recently, the role of IH in cancer has also been studied in the context of obstructive sleep apnea (OSA), since IH is a hallmark characteristic of this condition. Such recent studies are undoubtedly adding more information regarding the role of IH on tumor malignancy. In terms of the IH patterns associated with OSA, this altered oxygenation paradigm has been recently proposed as a determinant factor in fostering cancer incidence and progression from both in vitro and in vivo experimental models. Here, we summarize all the available evidence to date linking IH effects on several types of cancer.

20 Review Circulating exosomes in obstructive sleep apnea as phenotypic biomarkers and mechanistic messengers of end-organ morbidity. 2018

Khalyfa, Abdelnaby / Kheirandish-Gozal, Leila / Gozal, David. ·Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. Electronic address: akhalyfa@uchicago.edu. · Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. ·Respir Physiol Neurobiol · Pubmed #28676332.

ABSTRACT: Obstructive sleep apnea (OSA), the most severe form of sleep disordered breathing, is characterized by intermittent hypoxia during sleep (IH), sleep fragmentation, and episodic hypercapnia. OSA is associated with increased risk for morbidity and mortality affecting cardiovascular, metabolic, and neurocognitive systems, and more recently with non-alcoholic fatty liver disease (NAFLD) and cancer-related deaths. Substantial variability in OSA outcomes suggests that genetically-determined and environmental and lifestyle factors affect the phenotypic susceptibility to OSA. Furthermore, OSA and obesity often co-exist and manifest activation of shared molecular end-organ injury mechanisms that if properly identified may represent potential therapeutic targets. A challenge in the development of non-invasive diagnostic assays in body fluids is the ability to identify clinically relevant biomarkers. Circulating extracellular vesicles (EVs) include a heterogeneous population of vesicular structures including exosomes, prostasomes, microvesicles (MVs), ectosomes and oncosomes, and are classified based on their size, shape and membrane surface composition. Of these, exosomes (30-100nm) are very small membrane vesicles derived from multi-vesicular bodies or from the plasma membrane and play important roles in mediating cell-cell communication via cargo that includes lipids, proteins, mRNAs, miRNAs and DNA. We have recently identified a unique cluster of exosomal miRNAs in both humans and rodents exposed to intermittent hypoxia as well as in patients with OSA with divergent morbid phenotypes. Here we summarize such recent findings, and will focus on exosomal miRNAs in both adult and children which mediate intercellular communication relevant to OSA and endothelial dysfunction, and their potential value as diagnostic and prognostic biomarkers.

21 Review Association between sleep apnea and low bone mass in adults: a systematic review and meta-analysis. 2017

Eimar, H / Saltaji, H / Ghorashi, S / Isfeld, D / MacLean, J E / Gozal, D / Graf, D / Flores-Mir, C. ·School of Dentistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, T6G 1C9, Canada. Eimar@ualberta.ca. · School of Dentistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, T6G 1C9, Canada. · Private Practice, Tehran, Iran. · Division of Respiratory Medicine, Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, T6G 1C9, Canada. · Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, 60637, USA. ·Osteoporos Int · Pubmed #28101630.

ABSTRACT: We performed a systematic review of the literature to assess the association between sleep apnea and bone metabolism diseases including osteoporosis in adult population. Results from clinical trials suggest that the association between sleep apnea and low bone mass in adults is possible. INTRODUCTION: This study aimed to synthesize existing evidence on the potential association between sleep apnea and low bone mass in adults. METHODS: Electronic searches of five databases were performed. The inclusion criteria consisted of studies in humans that assessed potential associations between sleep apnea and bone metabolic diseases in an adult population. For diagnosis of sleep apnea overnight polysomnography, home polygraphy, or validated records from healthcare databases were considered. Reduced bone density, osteoporosis, serum/urinary levels for markers of bone formation and resorption, or risk of fractures caused without history of trauma were considered indicators of low bone mass. A random-effects model meta-analysis was applied when possible. RESULTS: Of the 963 relevant references, 12 studies met our inclusion criteria and were assessed to be of medium to low bias. Nine out of 12 studies reported an association between sleep apnea and low bone mass (increased bone resorption markers, reduced bone density, and higher risk of osteoporosis). Two studies did not report a significant association, whereas one study reported an increase of bone density in sleep apnea patients compared to non-sleep apnea patients. Meta-analysis of 2 studies (n = 112,258 patients) showed that sleep apnea was a significant risk factor for osteoporosis (odds ratio (OR), 1.92; 95%CI, 1.24 to 2.97; I CONCLUSIONS: An association between sleep apnea and low bone mass in adults is plausible, but supporting evidence has a risk of bias and is inconsistent.

22 Review Gender dimorphism in pediatric OSA: Is it for real? 2017

Brockmann, Pablo E / Koren, Dorit / Kheirandish-Gozal, Leila / Gozal, David. ·Department of Pediatric Cardiology and Pulmonology, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Sleep Medicine Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. · Sections of Pediatric Sleep Medicine and Pulmonology, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA; Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Department of Medicine, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. · Sections of Pediatric Sleep Medicine and Pulmonology, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. Electronic address: dgozal@uchicago.edu. · Sections of Pediatric Sleep Medicine and Pulmonology, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. ·Respir Physiol Neurobiol · Pubmed #27890604.

ABSTRACT: In epidemiologic studies focused on adults, obstructive sleep apnea (OSA) has higher prevalence in men than in women. The evidence supporting a gender-related discrepant prevalence of OSA is however much more tenuous in children. Here, we aimed to review the evidence concerning gender- based differences in the prevalence of OSA in children, and if so, to examine the evidence with the intent to identify potential factors that may account for this putative association. Gender-based perception and reporting of clinical manifestations of OSA may be modulated by several social and cultural factors in children. Among those factors, gender may crucially affect the reporting of symptoms such as snoring, and therefore markedly skew the male:female prevalence ratios of OSA. On the other hand, hormonal changes associated with puberty, may be playing a role, albeit a relatively smaller one than previously construed. Gender bias in OSA is most likely due to complex interactions between several physiological and epidemiologic factors that are clearly operational in adults. However, the evidence of clear gender-based differences in OSA prevalence or severity remains unclear in pre-pubertal children, and may be detectable in adolescents only when concurrent obesity is also present. Furthermore, no published evidence emerged supporting increased susceptibility to OSA-related in pre-pubertal boys vs. girls, except in obese adolescents or in girls with elevated testosterone levels. Future research in OSA may give clues on the role of gender-related hormonal changes as a modulating factor in childhood.

23 Review Pediatric OSA Syndrome Morbidity Biomarkers: The Hunt Is Finally On! 2017

Kheirandish-Gozal, Leila / Gozal, David. ·Section of Pediatric Sleep Medicine, Department of Pediatrics, Biological Sciences Division, Pritzker School of Medicine, The University of Chicago, Chicago, IL. Electronic address: lgozal@peds.bsd.uchicago.edu. · Section of Pediatric Sleep Medicine, Department of Pediatrics, Biological Sciences Division, Pritzker School of Medicine, The University of Chicago, Chicago, IL. ·Chest · Pubmed #27720883.

ABSTRACT: Since initial reports 40 years ago on pediatric OSA syndrome (OSAS) as a distinct and prevalent clinical entity, substantial advances have occurred in the delineation of diagnostic and treatment approaches. However, despite emerging and compelling evidence that OSAS increases the risk for cognitive, cardiovascular, and metabolic end-organ morbidities, routine assessment of such morbidities is seldom conducted in clinical practice. One of the major reasons for such discrepancies resides in the relatively labor-intensive and onerous steps that would be required to detect the presence of any of such morbidities, further adding to the already elevated cost of diagnosing the disorder. To circumvent these obstacles, the search for biomarker signatures of pediatric OSA and its cognitive and cardiometabolic consequences was launched, and considerable progress has occurred since then. Here, we review the current evidence for the presence of morbidity-related biomarkers among children with OSAS, and explore future opportunities in this promising arena.

24 Review Sleep and Breathing … and Cancer? 2016

Owens, Robert L / Gold, Kathryn A / Gozal, David / Peppard, Paul E / Jun, Jonathan C / Dannenberg, Andrew J / Lippman, Scott M / Malhotra, Atul / Anonymous5000880. ·Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, California. rowens@ucsd.edu. · Moores Cancer Center, University of California San Diego, La Jolla, California. · Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois. · Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. · Division of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, California. ·Cancer Prev Res (Phila) · Pubmed #27604751.

ABSTRACT: Sleep, like eating and breathing, is an essential part of the daily life cycle. Although the science is still emerging, sleep plays an important role in immune, cardiovascular, and neurocognitive function. Despite its great importance, nearly 40% of U.S. adults experience problems with sleep ranging from insufficient total sleep time, trouble initiating or maintaining sleep (Insomnia), circadian rhythm disorders, sleep-related movement disorders, and sleep-related breathing disorders such as obstructive sleep apnea (OSA). Herein, we discuss new evidence that suggests that sleep may also affect carcinogenesis. Specifically, we review recent epidemiologic data suggesting links between cancer and OSA. As OSA is a common, underdiagnosed, and undertreated condition, this has public health implications. Intriguing animal model data support a link between cancer and sleep/OSA, although mechanisms are not yet clear. Leaders in the fields of sleep medicine, pulmonology, and oncology recently met to review and discuss these data, as well as to outline future directions of study. We propose a multidisciplinary, three-pronged approach to studying the associations between cancer and sleep, utilizing mutually interactive epidemiologic studies, preclinical models, and early-phase clinical trials. Cancer Prev Res; 9(11); 821-7. ©2016 AACR.

25 Review The Challenges of Precision Medicine in Obstructive Sleep Apnea. 2016

Khalyfa, Abdelnaby / Gileles-Hillel, Alex / Gozal, David. ·Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. · Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. Electronic address: dgozal@uchicago.edu. ·Sleep Med Clin · Pubmed #27236058.

ABSTRACT: Obstructive sleep apnea (OSA) is a highly prevalent condition that remains underdiagnosed and undertreated. The onerous and labor-intensive nature of polysomnography or similar diagnostic multichannel-based approaches paves the way for exploration of biomarkers aimed at diagnosis, morbidity detection, and monitoring of therapy and its outcomes. To this effect, "Omics" technologies coupled with appropriate bioinformatic approaches should enable discovery of unique biomarker-based signatures, enabling simplified and highly precise algorithms for the evaluation and treatment of symptomatic individuals. Such approaches are likely to not only lead to improved outcomes but also permit personalized medicine to become reality in the context of OSA.

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