Severe Asthma Research Program (SARP)
A National Institutes of Health/ National Heart, Lung & Blood Institutes
sponsored network
Your Subtitle text
University of Pittsburgh info for Medical and Academic Professionals
The University of Pittsburgh site, headed by PI, Sally Wenzel, MD, is focused on the role of differences in the small airway in patients with severe asthma, and the inflammatory and repair processes which control these changes. Specific studies include the use of objective CT scan imaging to link airway disease and air trapping, the role of the mast cell and its phenotypes in different lung compartments and the link with overall inflammatory patterns. In addition, the University of Pittsburgh site has focused on differences in severe asthma phenotypes, including those related to age at diagnosis of asthma, differences in male and female severe asthma, as well as the influence of genetic factors on these phenotypes.
Sally E. Wenzel, MD
Director, Asthma and Allergic Diseases Center
University of PIttsburgh/UPMC
NW 628 Montefiore
3459 Fifth Ave
Pittsburgh, PA
wenzelse@upmc.edu
Fax: 412-605-1999
Phone: 412-802-6859
412-692-2216
Research Interest:
Our laboratory has been interested in the pathogenesis of human asthma, and more specifically, severe asthma for nearly 20 years. To this end, we have 3 ongoing areas of interest ranging from clinical and genetic epidemiologic studies to airway pathobiology and cell biology.
Studies on the phenotypes of severe asthma. Asthma is not a single disease, rather, it consists of several different phenotypes. We participate as one of 4 NIH sponsored sites to investigate the pathogenesis of severe asthma. This network has collected a database of 1000 asthmatics of varying severity which includes questionnaire, genetic, physiologic, immunologic and pathologic components. As part of these studies, we are performing extensive pathologic analysis of airway inflammatory/immune processes in the asthmatic (and control) lung. These data are constantly being analyzed to evaluate the various phenotypes and, more recently, the related genotypes that make up "asthma", with the ultimate goal of enhancing patient care.
The impact of Th2 pathway activation in cells of interest in asthma. These studies are done on primary human lung cells obtained during bronchoscopy and are thus unique in their ability to reflect the human condition. Our laboratory is extremely interested in the airway epithelial cell changes in response to IL-13 stimulation, including induction of iNOS (only seen in primary human airway epithelial cells), the 15 lipoxygenase pathway and a relatively new (to lung biology) pathway, that of 15 prostaglandin dehydrogenase. These pathways are being investigated for both upstream signaling events, as well as the downstream effects on inflammation and mucus production. Air liquid interface systems, siRNA and lentivirus transfection systems are used to perform these studies.
In addition to epithelial cell responses, our laboratory is investigating similar Th2 effects on proximal and distal lung fibroblasts, alone and in combination with transforming growth factor-beta. Similar to the epithelial cell studies, siRNA/dominant negative expression technologies have been successfully used in primary cell culture.
The impact of viral infections in asthma exacerbations. These studies are being performed both in human subjects and in cell culture model systems. Sputum and blood are being collected from asthma subjects during asthma exacerbations and with resolution. We are exploring the impact of viral infection on eicosanoid and autophagic pathways. In vitro, rhinovirus is being added to epithelial cell cultures from asthmatic and normal subjects to compare various responses.
Recent Publication
Kotaru C, Schoonover KJ, Trudeau JB, Huynh ML, Zhou X, Hu H, Wenzel SE. Regional fibroblast heterogeneity in the lung: implications for remodeling. Am J Respir Crit Care Med; 173(11): 1208-15, 2006
Trudeau J, Hu H, Chibana K, Chu HW, Westcott JY, Wenzel SE. Selective downregulation of prostaglandin E2-related pathways by the Th2 cytokine IL-13. J Allergy Clin Immunol; 117(6): 1446-54, 2006.
Wenzel SE. Asthma: Defining of the Persistent Adult Phenotypes. Lancet; 368: 804-13, 2006
Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, Calhoun WJ, Castro M, Chung KF, Clark MP, Dweik RA, Fitzpatrick AM, Gaston B, Hew M, Hussain I, Jarjour NN, Israel E, Levy BD, Murphy JR, Peters SP, Teague WG, Meyers DA, Busse WW, Wenzel SE; for the NHLBI's Severe Asthma Research Program. Characterization of the severe asthma phenotype by the Natinal Heart, Lung, and Blood Institute's Severe Asthma Research Program J Allergy Clin Immuno. 2007; Feb;119(2):405-413
Wenzel SE, Balzar S, Ampleford E, Hawkins GA, Busse WW, Calhoun WJ, Castro M, Chung KF, Erzurum S, Gaston B, Israel E, Teague WG, Curran-Everett D, Meyers DA, Bleecker ER. IL-4R(alpha) Mutations are Associated with Asthma Exacerbations and Mast Cells/IgE Expression. Am J Respir Crit Care Med. 2007; 175: 570-576.
Balzar S, Strand, M, Rhodes D, Wenzel S. IgE expression pattern in lung: Relation to systemic IgE and asthma phenotypes. J Allergy Clin Immunol 2007; 119: 855-62.
Zhou X. Hu H. Huynh M. Kotaru C. Balzar S. Trudeau J. Wenzel SE. Mechanisms of tissue inhibitor of metalloproteinase - 1 augmentation by IL-13 on TGF-stimulated primary human fibroblasts. J Allergy Clin Immunol 2007; 119: 1388-97.
Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet. 2007 Oct 20;370(9596):1396-8.
