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		Search Text: Home/< Back ToThe Science/Asthma and Lung Inflammation
  Asthma and Lung Inflammation
    The Laboratory of Asthma and Lung Inflammation, led by Dr. Stewart Levine, is focused on developing new treatment approaches for patients with severe asthma.
    On This Page
    
          S. Levine
  Stewart Levine, M.D.
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              Asthma is a common disease that affects 300 million people worldwide. The pathogenesis of asthma involves airway inflammation, as well as airway remodeling and hyperreactivity, which leads to difficulty in breathing which can be deadly if not properly controlled. Steroid medications can successfully treat asthma in most cases. However, the side-effects of long-term steroid administration can be profound, and in the approximately 5% of patients with severe refractory asthma, these medications fail to adequately control the disease. Dr. Levine is focused on developing new treatment approaches for patients with severe asthma.

In a mouse model of experimental asthma, Dr. Levine's laboratory exposed mice to house dust mites (HDM). Using a genome-wide analysis of the lung transcriptome, Dr. Levine and colleagues have identified genes that are upregulated as a result of the disease and whose activity is not modulated by the administration of corticosteroids. Of the 68 steroid-unresponsive genes discovered through this approach, the Levine laboratory initially focused on one that had not been previously implicated in the pathogenesis of asthma, apolipoprotein E (ApoE).

Dr. Levine’s group has shown that ApoE, which is made by macrophages in the lung, binds to low density lipoprotein receptors (LDLR) that are expressed by ciliated airway epithelial cells. In doing so, ApoE attenuates airway remodeling (mucous cell metaplasia) and airway hyperreactivity. Moreover, he has demonstrated that the administration of a small ApoE mimetic peptide to HDM-challenged mice markedly attenuates the three key pathogenic features of asthma: airway inflammation, airway remodeling, and airway hyperreactivity.

In related studies, Dr. Levine is working with colleagues at the NHLBI to study the role of peptide mimetics of apolipoprotein A-I (apoA-I) in their murine model of asthma, as well as the role of apoA-I pathways in asthma pathogenesis. Dr. Levine’s group has extended these findings to asthmatics, where they have shown that increased serum levels of high-density lipoproteins and apoA-I are associated with less severe airflow obstruction. While furthering his research into the mechanisms that modulate disease severity in asthma, Dr. Levine is completing the next phase of preclinical work necessary to move the concept of an inhaled apoA-I mimetic peptide for the treatment of asthma from mouse models into the first human clinical trials.

A clinician-scientist, Dr. Levine supervises a clinical program to study severe asthma and advance promising experimental therapeutics toward patient use. He and his colleagues have an ongoing longitudinal study to better understand the progression of severe refractory asthma and its response to treatment. They also have a bronchoscopy study that allows them to collect fluid and cells from the lungs of asthmatics so that they can define the role of apolipoprotein pathways in the respiratory system. These studies will not only have direct clinical implications, but will also advance the basic side of Dr. Levine’s research program, leading to even further clinical progress and, eventually, the possibility of ensuring that everyone with asthma can manage it simply and effectively.
  Videos

            Related resources from the Laboratory of Asthma and Lung Inflammation
      
            Clinical Center Grand Rounds

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World Asthma Day Video



NHLBI Orloff Award 2015: Stewart Levine & Jay Chung
Clinical Trials and Studies
Longitudinal Observational Study of Severe Asthma
				Recruiting
											
											Adult, Older Adult
					
											All Genders
					
																		Accepting Healthy Volunteers

				Are you an adult who has had asthma for longer than a year? This study will gather general information over a 20-year period about people who have had asthma to understand why patients respond differently to treatment. To participate in this study, you must be age 18 or older, have been diagnosed with asthma for at least one year, and not have any other major conditions. This study is located in Bethesda, Maryland.Sample Collections From the Airways of Asthmatic Patients
				Recruiting
											
											Adult, Older Adult
					
											All Genders
					
																		Accepting Healthy Volunteers

				Do you have asthma or would you like to help research on asthma? This study will look at the differences between cells from the airways of people who do and do not have asthma. Doctors will use a procedure called bronchoscopy to collect cells. To participate in this study, you must be between 18 and 75 years old, not have HIV, and not be pregnant or planning to become pregnant. This study is located in Bethesda, Maryland.Research Respiratory Tract Procedures
				Recruiting
											
											All Ages
					
											All Genders
					
																		Accepting Healthy Volunteers

				Are you a healthy adult or someone with a history of lung infections such as pneumonia or bronchitis? This study aims to compare fluid and tissue samples from the nose and lungs of healthy adults with people who have a lung disease. Researchers hope to learn why some people are more susceptible to certain infections. This study is located at the NIH Clinical Center in Bethesda, Maryland.Characterization of Tissue-Specific Immune Responses to Bronchoscopic Instillation of Mycobacterial Antigens into the Human Lung
				Recruiting
											
											Adult
					
											All Genders
					
																		Accepting Healthy Volunteers

				Are you an adult who has been exposed to tuberculosis (TB) or wants to help people who have? This study aims to learn how cells within the lungs react when exposed to Tuberculin Purified Protein Derivative, a compound that is commonly used to test for TB exposure. To participate in this study, you must be between the ages of 18 and 64 years old and have either been exposed to TB, but do not have active symptoms, or have never been exposed to TB. This study is located at the NIH Clinical Center in Bethesda, Maryland.Natural History of Bronchiectasis
				Recruiting
											
											All Ages
					
											All Genders
					
																		Accepting Healthy Volunteers

				Do you have bronchiectasis and get frequent lung infections? This study is exploring what causes frequent lung infections in people with bronchiectasis. Researchers will look at whether changes to a person's genes or immune system can raise the risk of these frequent infections. Participants in this study must be at least 5 years old and either healthy, diagnosed with bronchiectasis, or have a history of frequent lung infections. This study is located at the NIH Clinical Center in Bethesda, Maryland.Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults
				Recruiting
											
											Child, Adult
					
											All Genders
					
																		Not Accepting Healthy Volunteers

				Do you have symptoms of a lung disease (such as long-term wet cough, bronchiectasis, or recurrent pneumonia) with no genetic diagnosis? This study aims to develop new ways to diagnose primary ciliary dyskinesia (PCD) or primary immune deficiency (PID), two conditions that can have similar symptoms. Researchers will combine information from genetic testing, lung imaging, and lung function tests to diagnose and tell the difference between these two conditions. Participants in this study must be 5 to 45 years old and must have symptoms of a serious lung disease but no diagnosis. This study is taking place at multiple locations in the United States and in Canada, including the NIH Clinical Center in Bethesda, Maryland.
Featured Publications
                Apolipoprotein E Signals via TLR4 to Induce CXCL5 Secretion by Asthmatic Airway Epithelial Cells
            Authors:Kalchiem-Dekel O, Yao X, Barochia AV, Kaler M, Figueroa DM, Karkowsky WB, Gordon EM, Gao M, Fergusson MM, Qu X, Liu P, Li Y, Seifuddin F, Pirooznia M, Levine SJ.
                                                                                                                        
            Am J Respir Cell Mol Biol
      
                2020 Aug 01;63(2):185-197
        Read Publication
                      Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway
            Authors:Jaiswal AK, Makhija S, Stahr N, Sandey M, Suryawanshi A, Saxena A, Dagur PK, McCoy JP, Levine SJ, Mishra A.
                                                                                            
            Front Immunol 
      
                2020 Feb 28;11:363
        Read Publication
                      Meeting the Challenge of Identifying New Treatments for Type 2-low Neutrophilic Asthma
            Authors:Kalchiem-Dekel O, Yao X, Levine SJ.
                                                                                                                        
            CHEST
      
                2020 Jan 01;157(1):26-33
        Read Publication
                      Apolipoprotein E Is a Concentration-Dependent Pulmonary Danger Signal That Activates the NLRP3 Inflammasome and IL-1β Secretion by Bronchoalveolar Fluid Macrophages From Asthmatic Subjects
            Authors:Gordon EM, Yao X, Xu H, Karkowsky W, Kaler M, Kalchiem-Dekel O, Barochia AV, Gao M, Keeran KJ, Jeffries KR, Levine SJ.
                                                                                                                        
            J Allergy Clin Immunol.
      
                2019 Aug 01;144(2):426-441
        Read Publication
                      The APOE ε4 Allele Is Associated With a Reduction in FEV1/FVC in Women: A Cross-Sectional Analysis of the Long Life Family Study
            Authors:Kulminski AM, Barochia AV, Loika Y, Raghavachari N, Arbeev KG, Wojczynski MK, Thyagarajan B, Vardarajan BN, Christensen K, Yashin AI, Levine SJ.
                                                                                                                        
            PLoS One.
      
                2018 Nov 08;13(11):e0206873
        Read Publication
  Meet the Team

    S. Levine

            Stewart Levine, M.D.
                Senior Investigator
                Stewart Levine received his M.D. from the State University of New York at Stony Brook School of Medicine in 1983. He did his internship and residency in internal medicine at St. Vincent’s Hospital and Medical Center in New York City and fellowships in pulmonary medicine at Memorial Sloan-Kettering Cancer Center from 1986 to 1988 and critical care medicine at the NIH from 1989 to 1995. He joined the NIH as a staff clinician in the Critical Care Medicine Department of the Clinical Center in 1995, became a tenure-track Investigator in the NHLBI in 1998, and was promoted to Senior Investigator in 2007. He also served as a Medical Officer in the United States Public Health Service and was the Medical Director of the NHLBI’s Upper Cardozo Pulmonary Clinic. Dr. Levine received the NHLBI Division of Intramural Research Orloff Science Award twice in 2012 and again in 2015. In 2015, he also received the NHLBI Director’s Outstanding Translational Science Award. He has authored or coauthored more than 100 publications. He is a member of the editorial boards of the American Journal of Respiratory Cell and Molecular Biology and Frontiers in Immunology, and has previously served on the editorial boards of the Journal of Biological Chemistry and Chest. He is a member of the American Society for Clinical Investigation, American Thoracic Society, American College of Chest Physicians, American Association for the Advancement of Science, and American Society for Biochemistry and Molecular Biology. He is a member of the NIH Institutional Review Board and previously served as Vice President of the Metropolitan D.C. Thoracic Society. Additionally, he holds two patents from his work.

NHLBI Orloff Award 2015: Stewart Levine & Jay Chung
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                    301-402-1448
                Fax:
            301-451-5633
  Amisha
    
            Amisha Barochia, M.D.
        

    Staff Clinician

        barochiaav@mail.nih.gov
            Joni
    
            Joni  Mills, C.R.N.P.
        

    Nurse Practitioner
            Xianglan
    
            Xianglan Yao, M.D., Ph.D.
        

    Staff Scientist

        yaox2@mail.nih.gov
            Xuan (Lily)  Qu, M.D.
        

    Senior Research Assistant
            D. Figueroa Irizarry
    
            Debbie Figueroa Irizarry, Ph.D.
        

    Postdoctoral Fellow

        debbie.figueroa@nih.gov
            Karkowsk
    
            William  Karkowsk, M.D.
        

    Postdoctoral Fellow
            Maria
    
            Maria  Trinidad Soria Florido, Ph.D.
        

    Postdoctoral Fellow
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