Mount Sinai Study Finds One Quarter of WTC Responders Continue to Have Lung Function Impairment
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Dr. Gwen Skloot discusses the link between asthma and obesity in The Daily News feature The Daily Check Up.
Critical Care Medicine
MD, New York University
Internship, Internal Medicine
Mount Sinai Hospital
Residency, Internal Medicine
Mount Sinai Hospital
Fellowship, Pulm & Critical Care
Johns Hopkins Hospital
Airway Responsiveness in Asthma
Our laboratory focuses on clinical asthma studies. We hypothesize that hyperresponsiveness is caused by impairment in the ability of inspiration to stretch airway smooth muscle (ASM) -- i.e. impaired bronchodilation. This hypothesis is supported by our finding that sensitivity to the constrictor agent Methacholine is the same in normals and asthmatics when challenge is conducted without deep breaths. It is also known that deep inspiration (DI) prior to a constrictor agent is bronchoprotective in normal subjects. We have shown that this effect relates to inspiratory velocity, i.e. a fast DI is more bronchoprotective than a slow DI. We speculate that in healthy subjects, DI stretches ASM and breaks cross bridges and that cross bridge breakage is enhanced with increased inspiratory velocity. In asthmatics, inflammation may impair this ability. Further protocols will focus on the mechanism of the impaired response to DI in asthma in order to ultimately develop interventions to treat this aspect of hyperresponsiveness.
We have developed an in vitro model to test similar ideas. We hypothesize that stretching guinea pig (GP) tracheal smooth muscle releases a humoral "relaxant" factor [i.e. stretch-induced relaxation (SIR) involves a receptor-mediated mechanism]. The analogous in vivo situation may be the release of a "bronchodilating" substance when a normal subject takes a deep breath. This bronchodilating substance may be decreased in asthma. We have demonstrated that GP tracheal smooth muscle does relax when stretched; this relaxation is enhanced post-carbachol. We have characterized this relaxation response by pharmacokinetic studies. Additional characterization studies are focused on inhibiting the SIR response with agents such as beta-blockers, indomethacin, etc. We have shown that after induction of airway inflammation, the SIR response is reduced. Future protocols will address the mechanism of this reduced response and the relevance to human asthma.
A Multi-Centre Open-Label Study of Mepolizumab in a Subset of Subjects with a History of Life Threatening/Seriously Debilitating Asthma Who Participated in the MEA115661 Trial
The purpose of this study is to allow subjects to continue to receive the study treatment they received in the existing GlaxoSmithKline (GSK) study MEA115661. The study medication mepolizumab is not approved by the Food and Drug Administration (FDA) for doctors to treat patients ...
Study MEA117106: Mepolizumab vs. Placebo as add-on treatment for frequently exacerbating COPD patients
The purpose of this study is to test an investigational (experimental) study medicine, called mepolizumab, to see if it is safe, and to see how effective it is at preventing COPD or Chronic Obstructive Pulmonary Disease exacerbations ('flare ups' of the condition). Mepolizumab is...
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Dr.Skloot did not report having any of the following types of financial relationships with industry during 2016 and/or 2017: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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