Severe Asthma Research Program    (SARP)
A National Institutes of Health/ National Heart, Lung & Blood Institutes
sponsored network

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University of Pittsburgh    info for Medical and Academic Professionals

Site Investigators and Locations:

 

Sally E Wenzel, M.D.; Principal Investigator & Steering Committee Chair
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



Fernando Holguin MD MPH; Co-Investigator
University of Pittsburgh
Pittsburgh, Pennsylvania 15213

  
Shean Aujla, MD; Co-Investigator
Children’s Hospital of Pittsburgh of UPMC
Pittsburgh, Pennslyvania, 15213

Site Coordinator Contacts:

 
University of Pittsburgh, Adult

Louise P. Martin, BSN, CCRC    
Phone: 412-692-4747
Fax: 412-605-1999    
Email: martinlp@upmc.edu

Jenelle Mock, BSN, CCRC    
Phone: 412-864-2219
Fax: 412-605-1999    
Email: mockjm@upmc.edu

 

Cathy Vitari, RN, BSN, AE-C   
Phone: 412-692-4747
Fax: 412-605-1999    
Email: vitarica@upmc.edu

 

Children’s Hospital of Pittsburgh of UPMC, Pediatrics

 

Paul Rebovich   
Phone: 412-692-5873   
Email: paul.rebovich@chp.edu 

Site Ancillary Study:
 DESCRIPTION: SARP l/ll recognized clinical/pathologic differences of severe asthma compared to milder asthma and identified distinct severe asthma phentoypes at baseline. Additional pathobiologic abnormalities were observed to occur in and across clusters which linked similarities in symptoms, exacerbation predilection, treatment, response. Yet, nothing is understood regarding the stability of implications of these clinical or pathologic phenotypes. Published SARP II data show that chymase positive mast cells (MCTC) predominate in the submucosa and epithelium in severe asthma, with evidence for an altered activation status. Preliminary data suggest that a luminal MCTC mRNA signature and activation pattern even better differentiates symptomatic and exacerbation prone severe from milder asthma. This MC signature is present across at least 2 of the 3 predominant severe asthma clusters. However, the mechanisms behind these changes, the interaction of these MCs with epithelial/inflammatory cells and their long term effects (and stability) are poorly understood. The goals of this application are to establish a longitudinal protocol capable of identifying asthma phenotypes and their long term implications in both adults and children with asthma and severe asthma, as well as evaluating their stability. This longitudinal protocol will intersect with mechanistic studies which identify a MCTC molecular phenotype, relate it to genetic characteristics as well as short/long term cellular, clinical, physiologic and radiologic outcomes and then analyze its stability over time. Finally, the proposal will mechanistically determine the impact of this mast cell signature on human airway epithelial cells. This innovative combination of in vitro/in vivo mechanistic and longitudinal molecular and clinical phenotyping is highly likely to uncover new molecular targets for severe asthma.

RELEVANCE: Severe asthma, impacts a minority of asthmatics, but accounts for a majority of the costs. While treatment of asthma has improved, severe asthma remains problematic and poorly treated. The proposed studies will identify new/novel molecular pathways, link them to baseline and longitudinal clinical, physiologic and radiologic outcomes and assess their stability over time leading to new molecular targets for therapy. 

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