Faculty Profile

D. Andrew Wellman, MD, PhD

David Andrew Wellman, MD
Associate Professor of Medicine, Harvard Medical School
Associate Physician, Sleep Division, Department of Medicine, Brigham and Women's Hospital

See publications


Address

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

Phone 617-783-8483
Fax 617-732-7337

Email awellman@rics.bwh.harvard.edu
Email BWHDSMadministration@partners.org

Society Memberships

American Thoracic Society
American Academy of Sleep Medicine

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

Mentor(s)

David P. White, MD

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
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 May 15. [Epub ahead of print] 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 Mar 11. [Epub ahead of print] 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. PMID: 26612386;  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.
PMID: 26612389;  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.
PMID: 26446124;  PMCID: PMC4712389.

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.
PMID: 25761982;  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.
PMID: 25515107;  PMCID: PMC4434563.

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. PMID: 25719754;  PMCID: PMC4418332.

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.
PMID: 25323235;  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. doi: 10.1152/japplphysiol.00259.2014. Epub 2014 Oct 16. 
PMID: 25324514;  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.
PMID: 25321848;  PMCID: PMC4315811.

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(20):4523-35. doi: 10.1113/jphysiol.2014.277210. Epub 2014 Aug 1.  PMID: 25085887;  PMCID: 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.
PMID: 25191791;  PMCID: PMC4299579.

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: PMC4131868.

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: PMC4098808.

Strohl KP, Wellman A. When CPAP is stopped: what are the "on switches" of sleep apnoea? Eur Respir J. 2014 May;43(5):1227-9. doi: 10.1183/09031936.00003614. PMID: 24789944.
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 Apr 15;116(8):1105-12. doi: 10.1152/japplphysiol.00853.2013. Epub 2014 Jan 23.
PMID: 24458746;  PMCID: PMC4035785.

Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep. 2014 Apr 1;37(4):811-9. doi: 10.5665/sleep.3596.
PMID: 24899767;  PMCID: PMC4044741.

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;  PMCID: PMC3977735.
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 Oct 15;188(8):996-1004. doi: 10.1164/rccm.201303-0448OC.
PMID: 23721582;  PMCID: PMC3826282.

Edwards BA, Wellman A, Owens RL. PSGs: more than just the AHI. J Clin Sleep Med. 2013 Jun 15;9(6):527-8. doi: 10.5664/jcsm.2738. PMID: 23772183;  PMCID: PMC3659370.
Butler JP, Owens RL, Malhotra A, Wellman A. Rebuttal from James P. Butler, Robert L. Owens, Atul Malhotra and Andrew Wellman. J Physiol. 2013 May 1;591(9):2237. doi: 10.1113/jphysiol.2013.253120. PMID: 23740882;  PMCID: PMC3650688.

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 May 1;591(9):2233-4. doi: 10.1113/jphysiol.2012.242297.
PMID: 23740880;  PMCID: PMC3650686.

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: PMC3543060.

Wellman A, Edwards BA, Sands SA, Owens RL, Nemati S, Butler J, Passaglia CL, Jackson AC, Malhotra A, White DP. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J Appl Physiol (1985). 2013 Apr;114(7):911-22. doi: 10.1152/japplphysiol.00747.2012. Epub 2013 Jan 24. PMID: 23349453;  PMCID: PMC3633440.

2012 Jun;13(6):663-7. doi: 10.1016/j.sleep.2012.02.012. Epub 2012 Apr 12. PMID: 22503005.
 
Malhotra A, Butler JP, Wellman A. The pharyngeal airway: is bigger really better? Chest. 2012 Jun;141(6):1372-5. doi: 10.1378/chest.11-2989. PMID: 22670014.

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 (1985). 2012 Sep 1;113(5):691-9. doi: 10.1152/japplphysiol.00091.2012. Epub 2012 May 24.
PMID: 22628372;  PMCID: PMC3472473.
 


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