Current/Ongoing Research Studies

  • CLINICAL TRIAL – AK001 for the treatment of nasal polyps

  • To see if you are eligible for any of our studies or for more information about the studies, please contact our Patient Coordinator, Marina Palumbo, at 617-525-1267 or via e-mail at mpalumbo3@partners.org.

     

    Past Research Studies

    Alcohol-induced Respiratory Symptoms Are Common in Patients With Aspirin Exacerbated Respiratory Disease.

    With this survey study, done in collaboration with Dr. White at the Scripps Clinic, we found that the prevalence of alcohol-induced upper (runny nose and/or nasal congestion) respiratory reactions in patients with AERD was 75% and the prevalence of alcohol-induced lower (wheezing and/or shortness of breath) respiratory reactions in AERD was 51%. These reactions were generally not specific to one type of alcohol and often occurred after ingestion of only a few sips of alcohol. Therefore we concluded that alcohol ingestion causes respiratory reactions in the majority of patients with AERD, and clinicians should be aware that these alcohol-induced reactions are significantly more common in AERD than in controls who are aspirin tolerant. The results of the study have been published in the Journal of Allergy & Clinical Immunology: In Practice.

    Prostaglandin E2 exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation

    Prostaglandin E2 (PGE2) is a chemical that is made by many cells in the body through the actions of the COX enzymes. PGE2 has the property of preventing the formation of leukotrienes and it therefore may be potentially beneficial in asthma and AERD. It is believed that patients with AERD may be especially susceptible to deletion of PGE2 levels when aspirin is administered. In this study, published in The Journal of Immunology in 2010, Lundequist and colleagues in the laboratory of Dr. Boyce demonstrated that murine models that lack the ability to make adequate levels of PGE2 develop severe eosinophilic inflammation in the lungs when they are exposed to house dust mite extract. This severe inflammation was prevented when the mice received experimental drugs that selectively stimulate the EP2 or EP3 receptors, which are proteins that permit cells to respond to to PGE2. This study suggests that EP2 and EP3 activating medications could be beneficial to patients with AERD when they become available for use in the clinic.

    LeukotriEne E4-induced pulmonary inflammation is mediated by the P2Y12 receptor

    Leukotriene E4 (LTE4) is present at very high levels in the respiratory tissues and urine of patients with AERD. For reasons that are unknown, patients with AERD are much more sensitive to wheezing and inflammation caused by LTE4 than asthmatic patients who do not have AERD. This study, done by Dr. Parachuri and colleagues in the laboratory of Dr. Boyce, was published in 2009 in The Journal of Experimental Medicine, showed that LTE4, in contrast to the other leukotrienes, does not work through the receptors for leukotrienes that are blocked by montelukast or other available asthma drugs. Instead, LTE4 acts through platelets and P2Y12 receptors (the targets of certain antiplatelet drugs that are used to prevent heart attacks and strokes) to promote inflammation and airway damage in mice. Thus, the P2Y12 receptor could be a therapeutic target for asthma. This may be especially true in AERD, since that disease is associated with both high levels of LTE4 in the urine and hyperresponsiveness to LTE4

    Cysteinyl leukotriene overproduction in aspirin exacerbated respiratory disease is driven by platelet-adherent leukocytes

    This study, done by Dr. Laidlaw and colleagues in the laboratory of Dr. Boyce, was published in 2012 by the journal Blood, investigated the role of platelet-adherent white blood cells (leukocytes) in cysteinyl leukotriene overproduction in patients with AERD. Increased percentages of neutrophils, eosinophils, and monocytes with adherent platelets were found in the blood of patients with AERD when compared with those seen in aspirin-tolerant control subjects. The adherent platelets resulted in higher levels of cysteinyl leukotriene production by activated granulocytes. The levels of LTE4 in the urine (which is one of the predictors of how severe a reaction to aspirin may be in a patient with AERD) were strongly correlated with the frequency of circulating platelet-adherent granulocytes in the blood. This study suggests that platelets, which were not previously considered to play a role in AERD, may be a critical part of the process by which leukotrienes are over-produced in AERD. Because leukotrienes are thought to cause many of the signs and symptoms of AERD, the authors speculated that antiplatelet therapies might be useful as treatment for AERD. Such therapies are part of the focus of our clinical trials.