UPMC Physician Resources

CYSTIC FIBROSIS AND BRONCHIECTASIS

About Us
The Adult Cystic Fibrosis Program at UPMC is the only comprehensive therapy program for patients with this disorder in western Pennsylvania. In addition to routine care for adults with Cystic Fibrosis (CF) , the program is active in the pre-transplant care of patients with advanced CF from across the country. The program is integrated with the Antonio J. and Janet Palumbo Cystic Fibrosis Center at Children’s Hospital of Pittsburgh of UPMC.

The Cystic Fibrosis Research Center at the University of Pittsburgh provides procedures for identifying functional outcomes, monitored in terms of lung function, ion transport, or gene expression, for investigators involved with CF research. 


Program Overview
The primary goal of the Cystic Fibrosis Research Center is to provide improved treatments, and ultimately a cure, for cystic fibrosis This collaborative effort by investigators in the Departments of Cell Biology and Physiology, Medicine, and Pediatrics, seeks to use complementary strengths in the basic science of CFTR and epithelial ion transport, and to translate applied basic science knowledge to clinical investigations.

In order to achieve these goals centers of excellence have been established in three categories of CF: 

  • Cell and Molecular Biology of CF
  • Infection and Inflammation in CF
  • Clinical Studies in CF


Cell and Molecular Biology  
The majority of research is conducted using primary human airway cell cultures established from CF and non-CF tissues made available by the more than 100 lung transplants that are performed annually at UPMC.   State-of-the-art biochemistry, molecular biology, cell biology, and electrophysiology are used to study CFTR and ENaC functions in epithelial membranes, how these pathways contribute to normal airway function, how they are trafficked between various compartments of the protein secretory and recycling pathways, and how therapeutic approaches can be derived from this understanding of channel function.  Most of this activity is currently supported by a NIH P30 grant, a Research Development Program grant from The Cystic Fibrosis Foundation, and individual NIH R01 or Cystic Fibrosis Foundation (CFF) mechanisms of support.

Infection and Inflammation 
The course of CF changes qualitatively when patients become colonized by opportunistic infections.  This area of research is designed to determine inflammatory response to chronic Pseudomonas aeruginosa and Aspergillus fumigatus infections, the cytokines that mediate this response, the host defense mechanisms that attempt to clear bacteria from the lung and the disease, and bacterial mechanisms responsible for clearance failure.  The response to pro-inflammatory cytokines may contribute to lung injury during sustained infection.  Thus, it is of critical importance to understand the interrelationship between the CFTR defect and host immunity to: 

  1. Improve our understanding of the pathogenesis of the diseases 
  2. Define bio-markers which may be better surrogates of disease progression as well as novel outcome measures for future clinical trials 
  3. Identify potential CF-specific targets for anti-inflammatory therapy. This work is currently supported primarily by a NIH SCOR, R01 and CFF grants


Clinical Studies  
A critical issue in CF research is translation of laboratory findings to new therapies, particularly identification of the most appropriate and efficient endpoints for clinical trials.  The need for new outcome measurements for assessing CF therapies has been long recognized, and although progress has been made recently towards validation of induced sputum markers and the use of improved airway clearance methods, further refinement is needed. 

Investigators at the Cystic Fibrosis Research Center have focused efforts for several years on proof of principle nasal epithelial ion transport studies for new ion channel modulators, and more recently, on identifying surrogate endpoints for disease activity and short-term responses to new therapies aimed at overcoming defects in mucociliary clearance.  Collaborative investigations between Center investigators and scientists at Carnegie Mellon University have focused on improvements in airway clearance techniques and the use of surfactants as airway delivery reagents.  

Whole-lung mucociliary clearance measurements have been used successfully as a short-term outcome measure in previous studies, but new isotope methods are showing promise for assessing transepithelial airway liquid movements as a means to test therapeutics that target the basic defect in CFTR.  These studies are supported by the NIH, NSF, and the CF Foundation.