Faculty Profile

D. Andrew Wellman, MD, PhD

Wellman 20191219.jpg
Associate Professor of Medicine, Harvard Medical School

Administrative Title(s)

Director, Sleep Disordered Breathing Lab

See publications


Address

Division of Sleep Medicine
221 Longwood Avenue, Room 044 BLI
Boston, MA 02115

Phone 617-732-5721
Fax 617-732-7337

Email awellman@bwh.harvard.edu

Research Unit(s)

Sleep Disordered Breathing Lab

Research Interests

My research interest is in developing new therapies for sleep apnea through a better understanding of the pathophysiology. Sleep apnea is a multifactorial disorder due to: 1) a small (narrow lumen) pharyngeal airway, 2) an oversensitive ventilatory control system (leading to ventilatory overshoots and undershoots), 3) a poor pharyngeal muscle response during sleep, and 4) a low respiratory arousal threshold (wake up easily from mild airway obstruction). My early papers studied the role of ventilatory control sensitivity in sleep apnea, primarily in different subpopulations known to be at risk for this disease (elderly, male gender, individuals with a collapsible pharyngeal airway). These experiments were critical in establishing the pathophysiological importance of ventilatory control sensitivity in sleep apnea.

More recently, I have been applying engineering principles to develop new methods for measuring and modeling all four of the traits listed above. This work has been published in the Journal of Applied Physiology and describes a clinically feasible technique for determining the relative importance of each trait in a particular OSA patient. Such a technique has clinical importance, as it could lead to newer treatment approaches that target the abnormal underlying trait(s). My future goals are to identify simpler methods for phenotyping and to determine the effectiveness of non- continuous positive airway pressure (non-CPAP) therapies at manipulating, or fixing, the different traits.

My work on OSA phenotyping has been extended to include pharyngeal collapse mechanisms.  The airway in OSA patients is known to collapse at different sites, e.g., palate, tongue, lateral walls, and/or epiglottis.  Furthermore, there are effective devices/surgeries available for treating these sites, such as palatal surgery or mandibular advancement splints.  However, the effective administration of these devices/surgeries is severely limited by a lack of imaging procedures to identify the site of collapse; imaging must be performed during sleep and is too expensive or invasive for clinical use.  Meanwhile, my laboratory has correlated a variety of distinct flow shapes with the different sites of airway collapse.  Since airflow is easy to measure and is already collected during routine sleep studies, the analysis of these airflow patterns is a cheap and practical way to determine the site if obstruction and select the most appropriate non-CPAP therapy.  These studies are ongoing.

To make a donation to Dr. Wellman’s research lab, please click here.

Trainees

Robert Owens, MD
Shamim Nemati, PhD
Bradley Edwards, PhD
Scott Sands, PhD
Pedro Genta, MD, PhD
Luigi Taranto Montemurro, MD
Melania Marques, MD
Ali Azarbarzin, PhD
Camila de Melo, PhD
Yuan Haibo, MD
Sang-Wook Kim, MD
Ludovico Messineo, MD
Daniel Vena, PhD

Research Funding

2011-2017    Principal Investigator    NIH/NHLBI
R01 HL102321   
A method for measuring and modeling the physiologic traits causing sleep apneaThis grant describes a technique for measuring and modeling some of the important pathogenic traits causing sleep apnea. 

2015-2020    PI, Project 5    P01 HL095491   
Mechanisms of state switching in sleep and sleep apnea
This PPG includes basic and clinical projects to define the mechanisms underlying arousal and pharyngeal muscle activity in sleep apnea. Project 5 includes aims to pharmacologically target the pharyngeal muscles and arousal threshold to treat sleep apnea.

2016-2020    PI    R01 HL128658   
Clinical Methods for Determining the Site and Severity of Pharyngeal Collapse
The site of pharyngeal collapse in Sleep Apnea patients, as well as the collapsibility of the airway, will be made estimated using flow shape analysis

Selected Publications

Peer-Reviewed Publications
Bamagoos AA, Cistulli PA, Sutherland K, Madronio M, Eckert DJ, Hess L, Edwards BA, Wellman A, Sands SA. Polysomnographic Endotyping to Select Obstructive Sleep Apnea Patients for Oral Appliances. Ann Am Thorac Soc. 2019 Aug 9;. doi: 10.1513/AnnalsATS.201903-190OC. [Epub ahead of print] PubMed PMID: 31394914.

Messineo L, Taranto-Montemurro L, Azarbarzin A, Marques M, Calianese N, White DP, Wellman A, Sands SA. Loop gain in REM versus non-REM sleep using CPAP manipulation: A pilot study. Respirology. 2019 Aug;24(8):805-808. doi: 10.1111/resp.13608. Epub 2019 Jun 18. PubMed PMID: 31212392.

Mann DL, Terrill PI, Azarbarzin A, Mariani S, Franciosini A, Camassa A, Georgeson T, Marques M, Taranto-Montemurro L, Messineo L, Redline S, Wellman A, Sands SA. Quantifying the magnitude of pharyngeal obstruction during sleep using airflow shape. Eur Respir J. 2019 Jul;54(1). doi: 10.1183/13993003.02262-2018. Print 2019 Jul. PubMed PMID: 31000679.

Wellman A. Airway distensibility: Bringing physiology to the bedside. Respirology. 2019 Jun;24(6):607. doi: 10.1111/resp.13551. Epub 2019 Apr 3. PubMed PMID: 30945423.

Taranto-Montemurro L, Sands SA, Azarbarzin A, Wellman A. Reply to Patel and Althouse: Robust Methods Are Needed to Evaluate the Pharmacologic Treatment of Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2019 May 15;199(10):1295-1296. doi: 10.1164/rccm.201901-0072LE. PubMed PMID: 30807201; PubMed Central PMCID: PMC6519856.

Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, Eckert DJ, White DP, Wellman A. The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial. Am J Respir Crit Care Med. 2019 May 15;199(10):1267-1276. doi: 10.1164/rccm.201808-1493OC. PubMed PMID: 30395486; PubMed Central PMCID: PMC6519859.

Azarbarzin A, Sands SA, Taranto-Montemurro L, Redline S, Wellman A. Hypoxic burden captures sleep apnoea-specific nocturnal hypoxaemia. Eur Heart J. 2019 May 9;. doi: 10.1093/eurheartj/ehz274. [Epub ahead of print] PubMed PMID: 31071210.

Azarbarzin A, Sands SA, White DP, Redline S, Wellman A. The hypoxic burden: a novel sleep apnoea severity metric and a predictor of cardiovascular mortality-Reply to 'The hypoxic burden: also known as the desaturation severity parameter'. Eur Heart J. 2019 May 7;. doi: 10.1093/eurheartj/ehz273. [Epub ahead of print] PubMed PMID: 31065680.

Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019 Apr 7;40(14):1149-1157. doi: 10.1093/eurheartj/ehy624. PubMed PMID: 30376054; PubMed Central PMCID: PMC6451769.

Lim R, Carberry JC, Wellman A, Grunstein R, Eckert DJ. Reboxetine and hyoscine butylbromide improve upper airway function during non-REM and suppress REM sleep in healthy individuals. Sleep. 2018 Dec 27. doi: 10.1093/sleep/zsy261. [Epub ahead of print] PubMed PMID: 30590857.

Marques M, Genta PR, Azarbarzin A, Sands SA, Taranto-Montemurro L, Messineo L, White DP, Wellman A. Retropalatal and retroglossal airway compliance in patients with obstructive sleep apnea. Respir Physiol Neurobiol. 2018 Dec;258:98-103. doi: 10.1016/j.resp.2018.06.008. Epub 2018 Jun 18. PubMed PMID: 29913264; PubMed Central PMCID: PMC6251727.

Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, Eckert DJ, White DP, Wellman A.The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial. Am J Respir Crit Care Med. 2018 Nov 5. doi: 10.1164/rccm.201808-1493OC. [Epub ahead of print] PubMed PMID: 30395486.

Amatoury J, Jordan AS, Toson B, Nguyen C, Wellman A, Eckert DJ. New insights into the timing and potential mechanisms of respiratory-induced cortical arousals in obstructive sleep apnea. Sleep. 2018 Nov 1;41(11). doi: 10.1093/sleep/zsy160. PubMed PMID: 30137568; PubMed Central PMCID: PMC6231527.

Taranto-Montemurro L, Sands SA, Grace KP, Azarbarzin A, Messineo L, Salant R, White DP, Wellman DA. Neural memory of the genioglossus muscle during sleep is stage-dependent in healthy subjects and obstructive sleep apnoea patients. J Physiol. 2018 Nov;596(21):5163-5173. doi: 10.1113/JP276618. Epub 2018 Sep 4. PubMed PMID: 30022493; PubMed Central PMCID: PMC6209751.

Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2018 Oct 30. doi: 10.1093/eurheartj/ehy624. [Epub ahead of print] PubMed PMID: 30376054.

Butler MP, Emch JT, Rueschman M, Sands SA, Shea SA, Wellman A, Redline S. Apnea-Hypopnea Event Duration Predicts Mortality in Men and Women in the Sleep Heart Health Study. Am J Respir Crit Care Med. 2018 Oct 19. doi: 10.1164/rccm.201804-0758OC. [Epub ahead of print] PubMed PMID: 30336691.

Sands SA, Edwards BA, Terrill PI, Butler JP, Owens RL, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, Smales ET, de Melo CM, White DP, Malhotra A, Wellman A. Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy. Eur Respir J. 2018 Sep 27;52(3). pii: 1800674. doi: 10.1183/13993003.00674-2018. Print 2018 Sep. PubMed PMID: 30139771; PubMed Central PMCID: PMC6232193.

Messineo L, Taranto-Montemurro L, Azarbarzin A, Oliveira Marques MD, Calianese N, White DP, Sands SA, Wellman A.Breath-holding as a means to estimate the loop gain contribution to obstructive sleep apnoea. J Physiol. 2018 Sep;596(17):4043-4056. doi: 10.1113/JP276206. Epub 2018 Jul 6. PubMed PMID: 29882226; PubMed Central PMCID: PMC6117550.

Camassa A, Franciosini A, Sands SA, Zhi YX, Yadollahi A, Bianchi AM, Wellman A, Redline S, Azarbarzin A, Mariani S. Validating an Algorithm for Automatic Scoring of Inspiratory Flow Limitation Within a Range of Recording Settings. Conf Proc IEEE Eng Med Biol Soc. 2018 Jul;2018:4788-4791. doi: 10.1109/EMBC.2018.8513127. PubMed PMID: 30441417.

Zinchuk A, Edwards BA, Jeon S, Koo BB, Concato J, Sands S, Wellman A, Yaggi HK. Prevalence, Associated Clinical Features, and Impact on Continuous Positive Airway Pressure Use of a Low Respiratory Arousal Threshold Among Male United States Veterans With Obstructive Sleep Apnea. J Clin Sleep Med. 2018 May 15;14(5):809-817. doi: 10.5664/jcsm.7112. PubMed PMID: 29734986; PubMed Central PMCID: PMC5940432.

Sands SA, Edwards BA, Terrill PI, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, White DP, Wellman A. Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2018 May 1;197(9):1187-1197. doi: 10.1164/rccm.201707-1435OC. PubMed PMID: 29327943; PubMed Central PMCID: PMC6019932.

Chen H, Cade BE, Gleason KJ, Bjonnes AC, Stilp AM, Sofer T, Conomos MP, Ancoli-Israel S, Arens R, Azarbarzin A, Bell GI, Below JE, Chun S, Evans DS, Ewert R, Frazier-Wood AC, Gharib SA, Haba-Rubio J, Hagen EW, Heinzer R, Hillman DR, Johnson WC, Kutalik Z, Lane JM, Larkin EK, Lee SK, Liang J, Loredo JS, Mukherjee S, Palmer LJ, Papanicolaou GJ, Penzel T, Peppard PE, Post WS, Ramos AR, Rice K, Rotter JI, Sands SA, Shah NA, Shin C, Stone KL, Stubbe B, Sul JH, Tafti M, Taylor KD, Teumer A, Thornton TA, Tranah GJ, Wang C, Wang H, Warby SC, Wellman DA, Zee PC, Hanis CL, Laurie CC, Gottlieb DJ, Patel SR, Zhu X, Sunyaev SR, Saxena R, Lin X, Redline S. Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men. Am J Respir Cell Mol Biol. 2018 Mar;58(3):391-401. doi: 10.1165/rcmb.2017-0237OC. PubMed PMID: 29077507; PubMed Central PMCID: PMC5854957.

Azarbarzin A, Sands SA, Marques M, Genta PR, Taranto-Montemurro L, Messineo L, White DP, Wellman A. Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea. Eur Respir J. 2018 Feb 14;51(2). pii: 1701419. doi: 10.1183/13993003.01419-2017. Print 2018 Feb. PubMed PMID: 29444914; PubMed Central PMCID: PMC5915321.

Sands SA, Terrill PI, Edwards BA, Taranto Montemurro L, Azarbarzin A, Marques M, de Melo CM, Loring SH, Butler JP, White DP, Wellman A. Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea. Sleep. 2018 Jan 1;41(1). doi: 10.1093/sleep/zsx183. PubMed PMID: 29228393; PubMed Central PMCID: PMC5804982.

Messineo L, Taranto-Montemurro L, Sands SA, Oliveira Marques MD, Azabarzin A, Wellman DA. Broadband Sound Administration Improves Sleep Onset Latency in Healthy Subjects in a Model of Transient Insomnia. Front Neurol. 2017 Dec 21;8:718. doi: 10.3389/fneur.2017.00718. eCollection 2017. PubMed PMID: 29312136; PubMed Central PMCID: PMC5742584.

Kaur S, Wang JL, Ferrari L, Thankachan S, Kroeger D, Venner A, Lazarus M, Wellman A, Arrigoni E, Fuller PM, Saper CB. A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia. Neuron. 2017 Dec 6;96(5):1153-1167.e5. doi: 10.1016/j.neuron.2017.10.009. Epub 2017 Nov 2. PubMed PMID: 29103805; PubMed Central PMCID: PMC5720904.

Joosten SA, Landry SA, Sands SA, Terrill PI, Mann D, Andara C, Skuza E, Turton A, Berger P, Hamilton GS, Edwards BA. Dynamic loop gain increases upon adopting the supine body position during sleep in patients with obstructive sleep apnoea. Respirology. 2017 Nov;22(8):1662-1669. doi: 10.1111/resp.13108. Epub 2017 Jul 20. PubMed PMID: 28730724.

Chen H, Cade BE, Gleason KJ, Bjonnes AC, Stilp AM, Sofer T, Conomos MP, Ancoli-Israel S, Arens R, Azarbarzin A, Bell GI, Below JE, Chun S, Evans DS, Ewert R, Frazier-Wood AC, Gharib SA, Haba-Rubio J, Hagen EW, Heinzer R, Hillman DR, Johnson WC, Kutalik Z, Lane JM, Larkin EK, Lee SK, Liang J, Loredo JS, Mukherjee S, Palmer LJ, Papanicolaou GJ, Penzel T, Peppard PE, Post WS, Ramos AR, Rice K, Rotter JI, Sands SA, Shah NA, Shin C, Stone KL, Stubbe B, Sul JH, Tafti M, Taylor KD, Teumer A, Thornton TA, Tranah GJ, Wang C, Wang H, Warby SC, Wellman DA, Zee PC, Hanis CL, Laurie CC, Gottlieb DJ, Patel SR, Zhu X, Sunyaev SR, Saxena R, Lin X, Redline S. Multi-ethnic Meta-analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea Related Quantitative Trait Locus in Men. Am J Respir Cell Mol Biol. 2017 Oct 27. doi: 10.1165/rcmb.2017-0237OC. [Epub ahead of print] PubMed PMID: 29077507.

de Melo CM, Taranto-Montemurro L, Butler JP, White DP, Loring SH, Azarbarzin A, Marques M, Berger PJ, Wellman A, Sands SA. Stable Breathing in Patients With Obstructive Sleep Apnea Is Associated With Increased Effort but Not Lowered Metabolic Rate. Sleep. 2017 Oct 1;40(10). doi: 10.1093/sleep/zsx128. PubMed PMID: 28977669.

Azarbarzin A, Marques M, Sands SA, de Beeck SO, Genta PR, Taranto-Montemurro L, de Melo CM, Messineo L, Vanderveken OM, White DP, Wellman A. Predicting epiglottic collapse in patients with obstructive sleep apnoea. Eur Respir J. 2017 Sep 20;50(3). pii: 1700345. doi: 10.1183/13993003.00345-2017. Print 2017 Sep. PubMed PMID: 28931660.

Genta PR, Sands SA, Butler JP, Loring SH, Katz ES, Demko BG, Kezirian EJ, White DP, Wellman A. Airflow Shape Is Associated With the Pharyngeal Structure Causing OSA. Chest. 2017 Sep;152(3):537-546. doi: 10.1016/j.chest.2017.06.017. Epub 2017 Jun 23. PubMed PMID: 28651794.

Landry SA, Joosten SA, Sands SA, White DP, Malhotra A, Wellman A, Hamilton GS, Edwards BA. Response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient's therapeutic CPAP requirement. Respirology. 2017 Aug;22(6):1219-1224. doi: 10.1111/resp.13044. Epub 2017 Apr 13. PubMed PMID: 28409851; PubMed Central PMCID: PMC5511065.

Taranto-Montemurro L, Sands SA, Azarbarzin A, Marques M, de Melo CM, Edwards BA, Eckert DJ, Messineo L, White DP, Wellman A. Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults. Ann Am Thorac Soc. 2017 Jul;14(7):1177-1183. doi: 10.1513/AnnalsATS.201701-006OC. PubMed PMID: 28387543; PubMed Central PMCID: PMC5566293.

Souza FJFB, Genta PR, de Souza Filho AJ, Wellman A, Lorenzi-Filho G. The influence of head-of-bed elevation in patients with obstructive sleep apnea. Sleep Breath. 2017 Jun 24. doi: 10.1007/s11325-017-1524-3. [Epub ahead of print] PubMed PMID: 28647854.

Landry SA, Joosten SA, Eckert DJ, Jordan AS, Sands SA, White DP, Malhotra A, Wellman A, Hamilton GS, Edwards BA. Therapeutic CPAP Level Predicts Upper Airway Collapsibility in Patients With Obstructive Sleep Apnea. Sleep. 2017 Jun 1;40(6). doi: 10.1093/sleep/zsx056. PubMed PMID: 28419320.

Marques M, Genta PR, Sands SA, Azarbazin A, de Melo C, Taranto-Montemurro L, White DP, Wellman A. Effect of Sleeping Position on Upper Airway Patency in Obstructive Sleep Apnea Is Determined by the Pharyngeal Structure Causing Collapse. Sleep. 2017 Mar 1;40(3). doi: 10.1093/sleep/zsx005. PubMed PMID: 28329099.

Taranto-Montemurro L, Sands SA, Edwards BA, Azarbarzin A, Marques M, de Melo C, Eckert DJ, White DP, Wellman A. Effects of Tiagabine on Slow Wave Sleep and Arousal Threshold in Patients with Obstructive Sleep Apnea. Sleep. 2016 Nov 28. pii: sp-00422-16. [Epub ahead of print] PubMed PMID: 27923429.

Azarbarzin A, Sands SA, Taranto-Montemurro L, Oliveira Marques MD, Genta PR, Edwards BA, Butler J, White DP, Wellman A.Estimation of pharyngeal collapsibility during sleep by peak inspiratory airflow. Sleep. 2016 Sep 9. pii: sp-00130-16. [Epub ahead of print] PubMed PMID: 27634788.

Sands SA, Mebrate Y, Edwards BA, Nemati S, Manisty CH, Desai AS, Wellman A, Willson K, Francis DP, Butler JP, Malhotra A. Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. Am J Respir Crit Care Med.  2017 Jan 15;195(2):237-246.  PubMed PMID: 27559818.

Amatoury J, Azarbarzin A, Younes M, Jordan AS, Wellman A, Eckert DJ. Arousal Intensity is a Distinct Pathophysiological Trait in Obstructive Sleep Apnea. Sleep. 2016 Dec 1;39(12):2091-2100. doi: 10.5665/sleep.6304. PubMed PMID: 27784404; PubMed Central PMCID: PMC5103797.

Taranto-Montemurro L, Sands SA, Edwards BA, Eckert DJ, White DP, Wellman A. Reply: Is the Muscle the Only Potential Target of Desipramine in Obstructive Sleep Apnea Syndrome? Am J Respir Crit Care Med. 2017 Jun 15;195(12):1678-1679. doi: 10.1164/rccm.201701-0172LE. PubMed PMID: 28186830; PubMed Central PMCID: PMC5476916.

Taranto-Montemurro L, Sands SA, Edwards BA, Azarbarzin A, Marques M, de Melo C, Eckert DJ, White DP, Wellman A. Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation. Eur Respir J. 2016 Nov;48(5):1340-1350. doi: 10.1183/13993003.00823-2016. PubMed PMID: 27799387.

Edwards BA, Sands SA, Owens RL, Eckert DJ, Landry S, White DP, Malhotra A, Wellman A.The Combination of Supplemental Oxygen and a Hypnotic Markedly Improves Obstructive Sleep Apnea in Patients with a Mild to Moderate Upper Airway Collapsibility. Sleep. 2016 Nov 1;39(11):1973-83. PubMed PMID: 27634790.

Edwards BA, Andara C, Landry S, Sands SA, Joosten SA, Owens RL, White DP, Hamilton GS, Wellman A. Upper-airway Collapsibility and Loop Gain Predict the Response to Oral Appliance Therapy in Obstructive Sleep Apnea Patients. Am J Respir Crit Care Med. 2016 Dec. 1;194(11):1413-22. PubMed PMID: 27181367.

Taranto-Montemurro L, Edwards BA, Sands SA, Marques M, Eckert DJ, White DP, Wellman A. Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility During Non-REM Sleep in Healthy Subjects. Am J Respir Crit Care Med. 2016 Oct 1;194(7):878-885. PubMed PMID: 26967681.

Carberry JC, Jordan AS, White DP, Wellman A, Eckert DJ. Upper Airway Collapsibility (Pcrit) and Pharyngeal Dilator Muscle Activity are Sleep-Stage Dependent. Sleep. 2016 Mar 1;39(3):511-21. doi: 10.5665/sleep.5516. PubMed PMID: 26612386; PubMed Central PMCID: PMC4763361.

Nguyen CD, Wellman A, Jordan AS, Eckert DJ. Mild Airflow Limitation During N2 Sleep Increases K-complex Frequency and Slows Electroencephalographic Activity. Sleep. 2016 Mar 1;39(3):541-50. doi: 10.5665/sleep.5522. PubMed PMID: 26612389; PubMed Central PMCID: PMC4763368.

Genta PR, Edwards BA, Sands SA, Owens RL, Butler JP, Loring SH, White DP, Wellman A. Tube Law of the Pharyngeal Airway in Sleeping Patients with Obstructive Sleep Apnea. Sleep. 2016 Feb 1;39(2):337-43. doi: 10.5665/sleep.5440. PubMed PMID: 26446124; PubMed Central PMCID: PMC4712389.

Smales ET, Edwards BA, Deyoung PN, McSharry DG, Wellman A, Velasquez A, Owens R, Orr JE, Malhotra A. Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold. Ann Am Thorac Soc. 2015 May;12(5):758-64. doi: 10.1513/AnnalsATS.201408-399OC. PubMed PMID: 25719754; PubMed Central PMCID: PMC4418332.

Joosten SA, Edwards BA, Wellman A, Turton A, Skuza EM, Berger PJ, Hamilton GS. The Effect of Body Position on Physiological Factors that Contribute to Obstructive Sleep Apnea. Sleep. 2015 Sep 1;38(9):1469-78. doi: 10.5665/sleep.4992. PubMed PMID: 25761982; PubMed Central PMCID: PMC4531415.

Owens RL, Edwards BA, Eckert DJ, Jordan AS, Sands SA, Malhotra A, White DP, Loring SH, Butler JP, Wellman A.An Integrative Model of Physiological Traits Can be Used to Predict Obstructive Sleep Apnea and Response to Non Positive Airway Pressure Therapy. Sleep. 2015 Jun 1;38(6):961-70. doi: 10.5665/sleep.4750. PubMed PMID: 25515107; PubMed Central PMCID: PMC4434563.

Terrill PI, Edwards BA, Nemati S, Butler JP, Owens RL, Eckert DJ, White DP, Malhotra A, Wellman A, Sands SA. Quantifying the ventilatory control contribution to sleep apnoea using polysomnography. Eur Respir J. 2015 Feb;45(2):408-18. doi: 10.1183/09031936.00062914. Epub 2014 Oct 16. PubMed PMID: 25323235; PubMed Central PMCID: PMC4348093.

Wellman A, Genta PR, Owens RL, Edwards BA, Sands SA, Loring SH, White DP, Jackson AC, Pedersen OF, Butler JP. Test of the Starling resistor model in the human upper airway during sleep. J Appl Physiol (1985). 2014 Dec 15;117(12):1478-85. PMCID: PMC4269684.

Edwards BA, Eckert DJ, McSharry DG, Sands SA, Desai A, Kehlmann G, Bakker JP, Genta PR, Owens RL, White DP, Wellman A, Malhotra A. Clinical Predictors of the Respiratory Arousal Threshold in Patients with Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2014 Dec 1;190(11):1293-300. doi: 10.1164/rccm.201404-0718OC. PubMed PMID: 25321848; PubMed Central PMCID: PMC4315811.

Genta PR, Owens RL, Edwards BA, Sands SA, Eckert DJ, Butler JP, Loring SH, Malhotra A, Jackson AC, White DP, Wellman A. Influence of pharyngeal muscle activity on inspiratory negative effort dependence in the human upper airway. Respir Physiol Neurobiol. 2014 Sep 15;201:55-9. doi: 10.1016/j.resp.2014.07.005. Epub 2014 Jul 11. PMID: 25020212. PMCID: 4131868.

Gederi E, Nemati S, Edwards BA, Clifford GD, Malhotra A, Wellman A. Model-based estimation of loop gain using spontaneous breathing: A validation study. Respir Physiol Neurobiol. 2014 Sep 15;201:84-92. doi: 10.1016/j.resp.2014.07.002. Epub 2014 Jul 17. PMID: 25038522. PMCID: PMC4324174.

Edwards BA, Wellman A, Sands SA, Owens RL, Eckert DJ, White DP, Malhotra A. Obstructive sleep apnea in older adults is a distinctly different physiological phenotype. Sleep. 2014 Jul 1;37(7):1227-36. doi: 10.5665/sleep.3844. PMID: 25061251. PMCID: 4098808.

Edwards BA, Sands SA, Owens RL, White DP, Genta PR, Butler JP, Malhotra A, Wellman A. Effects of hyperoxia and hypoxia on the physiological traits responsible for obstructive sleep apnoea. J Physiol. 2014 Oct 15;592(Pt 20):4523-35. PMID: 25085887. PMC4287742.

Sands SA, Eckert DJ, Jordan AS, Edwards BA, Owens RL, Butler JP, Schwab RJ, Loring SH, Malhotra A, White DP, Wellman A. Enhanced Upper-airway Muscle Responsiveness is a Distinct Feature of Overweight/Obese Individuals Without Sleep Apnea. Am J Respir Crit Care Med. 2014 Oct 15;190(8):930-7. doi: 10.1164/rccm.201404-0783OC. PubMed PMID: 25191791; PubMed Central PMCID: PMC4299579.

Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Reply: Arousal threshold in obstructive sleep apnea. Am J Respir Crit Care Med. 2014 Feb 1;189(3):373-4. doi: 10.1164/rccm.201312-2115LE. PMID: 24484350. PMC3977735.

Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in obstructive sleep apnea patients with a low arousal threshold. SLEEP 2014;37(4):811-819. PMC4044741.

Owens RL, Edwards BA, Sands SA, Butler JP, Eckert DJ, White DP, Malhotra A, Wellman A.The classical starling resistor model often does not predict inspiratory airflow patterns in the human upper airway. J Appl Physiol (1985). 2014 Jan 23. 15; 116(8):1105-12. PMC4035785.

Butler JP, Owens RL, Malhotra A, Wellman A. Crosstalk opposing view: the human upper airway during sleep does not behave like a Starling resistor. J Physiol. 2013 591(pt 9): 2233-2234. PMCID: 3650686.

Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea: identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013 188(8): 996-1004. PMCID: 3826282.

Wellman A, Edwards BA, Sands SA, Owens RL, Nemati S, Butler JP, Passaglia CL, Jackson AC, Malhotra A, White DP. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J Appl Physiol. 2013 Apr; 114(7):911-22. PMID:23349453. PMCID: 3633440.

Edwards BA, Connolly JG, Campana LM, Sands SA, Trinder JA, White DP, Wellman A, Malhotra A. Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea. Sleep. 2013 Feb 1;36(2):281-5. doi: 10.5665/sleep.2390. PMID:23372276. PMCID: 3543060.

Owens RL, Edwards BA, Sands SA, Butler JP, Eckert DJ, White DP, Malhotra A, Wellman A. Upper airway collapsibility and patterns of flow limitation at constant end-expiratory lung volume. J Appl Physiol. 2012 May 24. PMID: 22628372. PMCID: 3472473.

Lovis A, De Riedmatten M, Greiner D, Lecciso G, Andries D, Scherrer U, Wellman A, Sartori C, Heinzer R. Effect of added dead space on sleep disordered breathing at high altitude. Sleep Med. 2012 Jun;13(6):663-7. Epub 2012 Apr 12. PMID: 22503005.

Edwards BA, Sands SA, Eckert DJ, White DP, Butler JP, Owens RL, Malhotra A, and Wellman A. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol. 2012 Mar; 590(Pt 5): 1199-211. Epub 2012 Jan 4. PMID: 22219335. PMCID: 3381825.

Jordan AS, Eckert DJ, Wellman A, Trinder JA, Malhotra A, White DP. Termination of respiratory events with and without cortical arousal in obstructive sleep apnea. Am J Respir Crit Care Med. 2011 Nov 15; 184(10): 1183-91. Epub 2011 Aug 11. PMID: L1836132. PMCID: 3262022.

Nemati S, Edwards BA, Sands SA, Berger PJ, Wellman A, Verghese GC, Malhotra A, Butler JP. Model-based characterization of ventilatory stability using spontaneous breathing. J Appl Physiol. 2011 Jul; 111(1): 55-67. Epub 2011 Apr 7. PMID: 21474696. PMCID: 3137535.

Wellman A, Eckert DJ, Jordan AS, Edwards BA, Passaglia CL, Jackson AC, Gautam S, Owens RL, Malhotra A, White DP. A method for measuring and modeling the physiological traits causing obstructive sleep apnea. J Appl Physiol. 2011 June; 110(6): 1627-37. Epub 2011 Mar 24. PMID: 21436459. PMCID: 3119134.

Eckert DJ, Owens RL, Kehlmann G, Wellman A, Rahangdale S, Yim-Yeh S, White DP, Malhotra A. Eszopiclone increases the respiratory arousal threshold and lowers the apnea/hypopnea index in obstructive sleep apnea patients with low arousal threshold. Clin Sci (Lond). 2011 Jun; 120(12):505-14. PMID: 21269278. PMCID: 3415379.

Jordan AS, White DP, Lo YL, Wellman A, Eckert DJ, Yim-Yeh S, Eikermann M, Smith SA, Stevenson KE, Malhotra A. Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. Sleep. 2009 Mar 1;32(3):361-8. PMCID: 2647790.

Wellman A, Malhotra A, Jordan AS, Stevenson KE, Gautam S, White DP. Effect of oxygen in obstructive sleep apnea: Role of loop gain. Respir Physiol Neurobiol. 2008;162(2):144-151.

Eikermann M, Jordan AS, Chamberlin NL, Gautam S, Wellman A, Lo YL, White DP, Malhotra A. The Influence of Aging on Pharyngeal Collapsibility During Sleep. Chest. 2007;131(6):1702-1709.

Wellman A, Malhotra A, Jordan AS, Schory K, Gautam S, White DP. Chemical control stability in the elderly. J Physiol. 2007;581(Pt 1):291-8.

Jordan AS, Wellman A, Heinzer RC, Lo YL, Schory K, Dover L, Gautam S, Malhotra A, White DP. Mechanisms Used To Restore Ventilation After Partial Upper Airway Collapse During Sleep In Humans. Thorax. 2007;62:861-867.

Lo YL, Jordan AS, Malhotra A, Wellman A, Heinzer RA, Eikerman M, Schory K, Dover L, White DP. The Influence of Wakefulness on Pharyngeal Airway Muscle Activity. Thorax. 2007;62:799-805.

Heinzer RC, Stanchina ML, Malhotra A, Jordan AS, Patel SR, Lo YL, Wellman A, Schory K, Dover L, White DP. Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea. Thorax. 2006;61(5):435-9.

Lo YL, Jordan AS, Malhotra A, Wellman A, Heinzer RC, Schory K, Dover L, Fogel RB, White DP. Genioglossal muscle response to CO2 stimulation during NREM sleep. Sleep. 2006;29(4):470-7.

Jordan AS, Wellman A, Edwards JK, Schory K, Dover L, MacDonald M, Patel SR, Fogel RB, Malhotra A, White DP. Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea. J Appl Physiol. 2005;99(5):2020-7.

Wellman A, Jordan AS, Malhotra A, Fogel RB, Katz ES, Schory K, Edwards JK, White DP. Ventilatory control and airway anatomy in obstructive sleep apnea. Am J Respir Crit Care Med. 2004;170(11):1225-32.

Moss M, Wellman DA, Cotsonis GA. An appraisal of multivariable logistic models in the pulmonary and critical care literature. Chest. 2003;123(3):923-8.

Wellman A, Malhotra A, Fogel RB, Edwards JK, Schory K, White DP. Respiratory system loop gain in normal men and women measured with proportional-assist ventilation. J Appl Physiol. 2003;94(1):205-12.

 


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