Atul Malhotra, M.D.
|Title||Associate Professor of Medicine|
|Institution||Brigham and Women's Hospital|
|Address||Brigham and Womens Hospital|
Pulmonary & Critical Care and Sleep Medicine Divisions
221 Longwood Ave
Boston MA 02115
1993||Intern of the Year|
1996||Gold Medal Outstanding Achievement for Medical Resident|
1994||Outstanding Teacher of Medical Students|
||Trainee Research Merit Award|
2002||Teacher of the Year|
2002||Teacher of the Year|
||Young Investigator Award|
||Teaching Appreciation Award from Pulmonary and Critical Care Fellows|
||Co-director Program of Distinction |
My work has helped to change our understanding of the disorder obstructive sleep apnea (OSA) from a single entity into a syndrome with multiple physiological etiologies. This critical expansion in knowledge should allow for the successful individualization of therapy. My group has taken our prior monolithic thinking about OSA elucidated at least three distinct disease pathways. The first, and most obvious, is abnormal upper airway anatomy. We demonstrated that a reduced airway length (from the hard palate to the epiglottis) is a key determinant of predisposition to OSA. Since women having a substantially shorter airway than men (76.1 vs. 58.2 mm, P<0001, independent of body size) this explains for the most part why women suffer from less frequent sleep apnea than men. This work goes beyond simple description, working with bioengineers, we developed a finite element computational model of the human airway that demonstrated the importance of airway length and other anatomical characteristics on OSA. This computational model and experimental measurements also quantified the effecting of aging on airway anatomy and physiology; thus providing a firm biomechanical basis for the previous clinical observations that indicate why OSA is common in the elderly. The second mechanism we have delineated is the control of pharyngeal dilator muscles. We have defined the critical stimuli controlling upper airway muscle activation (negative intrapharyngeal pressure, and C02) and delineated how these mechanisms are affected by sleep and aging. These studies have shown a marked attenuation in the protective airway reflex response to collapsing pressure (R=-0.55, p<0.005) and preferential deposition of fat around the pharyngeal airway, independent of systemic fat. These abnormalities combine to yield a pharyngeal airway which is mechanically unstable and vulnerable to collapse during sleep. One of the key control mechanisms that we have defined was ventilatory control instability (loop gain) which is a metric of the inherent instability in a ventilatory control system. This control system is inherently unstable in an easily definable subgroup of OSA patients. Furthermore, the effect of manipulating loop gain on apnea severity was also demonstrated by my lab making this a novel target for future therapies. We are also working to develop novel methods by which loop gain can be more easily measured in a clinical setting. Third I have shown that sleep state instability (a low arousal threshold to respiratory stimuli) predisposes an individual to cycling ventilation in the wake-sleep transition. That is, some patients develop unstable breathing as a result of an inability to stay asleep, since each arousal leads to marked increases in ventilation and fluctuations in carbon dioxide levels. Thus, the definable subgroup of sleep apnea patients with low arousal threshold may well respond favorably to certain hypnotic medications which will stabilize sleep without impairing respiratory muscles. I have recently completed a pilot clinical trial of hypnotic therapy in carefully selected OSA patients demonstrating clinically and statistically significant improvement in the apnea hypopnea index (Clinical Science (London) 2011) . This work has paved the way to pharmacological therapy for obstructive sleep apnea, one of the keys to moving us beyond CPAP (continuous positive airway pressure) therapy.
More recently, I have begun research involving the cardiovascular complications of sleep disorders, such as sleep apnea. I have received RO1 funding from NHLBI to perform experiments designed to identify those mechanisms important in linking sleep disorders with cardiovascular diseases. This work will help to define the components of sleep apnea that predispose to cardiovascular risk independent of comorbidities such as obesity. This work involves human subjects as well as cell culture and animal models.
My clinical responsibilities include teaching/attending in the Medical Intensive Care Unit, and directing the Clinical Sleep program at BWH. Over the past ten years, I have also attended in the Surgical Intensive Care Unit at BWH, the Medical Intensive Care Unit at MGH, the MICU at the BIDMC and seen patients in the Interstitial Lung Disease Clinic in the Center for Chest Disease at BWH. Most recently in 2012, I have attended in the surgical ICU at King Faisal Hospital in Kigali, Rwanda.
My teaching commitments include co-directing the HST 100 course in Respiratory Physiology and Pathophysiology, small group sessions for New Pathway students at HMS, resident lectures at MGH, BWH and BIDMC approximately once per week, and lecture the Pulmonary and Critical Care Fellows in the Harvard Combined Program on a weekly basis. I was recently director of the annual National Sleep Medicine Course for the AASM. I was also the Chairman of the Education Committee for the American Thoracic Society from 2005-2008. I am immediate past Chairman of the Sleep & Respiratory Neurobiology Assembly of the American Thoracic Society and a current Member of the Board of Directors of the ATS. I am co-director of the American Thoracic Society's Sleep State of the Art Course (SOTA). In total I give approximately 100 lectures per year.
In 2012, I was elected Secretary Treasurer of the American Thoracic Society and will thus be President of the American Thoracic Society in 2015.
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