Viral Pathogenesis of Early Cystic Fibrosis Lung Disease

Summary

Principal Investigator: SARATH CHANDRA RANGANATHAN
Abstract: DESCRIPTION (provided by applicant): The development and evolution of CF lung disease can be variable, but it is clear from our previous research that physiological and structural defects begin in infancy and are frequently present prior to the detection of bacterial infection, implicating other etiologies or infectious insults. Little is known about the impact of viruses on bacterial colonization, airway inflammation, physiological measures, and structural changes in the CF lung. In this proposal, we will define the role(s) of viral infections in the origins of eary CF pulmonary disease. Combining the expertise and resources available at the University of Indiana (Indianapolis, Indiana), Washington University (St. Louis, Missouri), and the Australian Early Surveillance Team for Cystic Fibrosis (AREST CF) (Melbourne and Perth, Australia), we will define the incidence and type of viral infections in CF infants. Bronchoalveolar lavage fluid and pharyngeal secretions will be collected at predetermined times during infancy, and highly sensitive nucleic acid-based detection and powerful microbiomic assays will be used to characterize lower respiratory tract infections. Also, we will systematically define the earliest physiological changes in the CF lung, combining analyses for inflammatory markers in lavage fluid, pulmonary function measurements, and computerized x-ray tomographic imaging, in a surveillance program for infants diagnosed shortly after newborn screening. Innovative airway modeling techniques will be applied to better detect and measure airway disease that precedes bronchiectasis. We will examine the relationship between viral infections and initial pathophysiological changes in the CF lung, and test the hypothesis that early respiratory viral infections alter the bacterial flora and inflammatory profile in the airway and accelerate progression of pulmonary disease in CF infants. The proposal has three Specific Aims, which will (i) define the frequency of respiratory virus infections and their impact on the evolution of endobronchial bacterial infection and inflammation in CF infants;(ii) examine the impact of early virus infections on the development of respiratory symptoms and physiological changes in the lungs of CF infants;and (iii) evaluate the relationship between virus infections and airway disease as de- fined by structural and airway modeling techniques. If successful, these studies will provide new insights into the pathogenesis of CF lung disease, aid the design of therapeutic strategies to reduce virus-induced pulmonary morbidity, and potentially prevent the development of irreversible airway disease. (End of Abstract)
Funding Period: 2012-09-26 - 2016-06-30
more information: NIH RePORT

Research Grants

  1. Improving Inhaled Drug Delivery with Self-dispersing Liquids
    STEPHEN GAROFF; Fiscal Year: 2013
  2. Cigarette Smoke and Susceptibility to Influenza Infection
    Terry L Noah; Fiscal Year: 2013
  3. Airway Inflammation and Airway Remodeling
    David H Broide; Fiscal Year: 2013
  4. MECHANISMS AND MODULATION OF ACCELLULAR HbA TOXICITY
    Joel M Friedman; Fiscal Year: 2013
  5. Primary Immune Deficiency Treatment Consortium
    Morton Cowan; Fiscal Year: 2013
  6. Novel approaches for vaccine design
    Michel C Nussenzweig; Fiscal Year: 2013
  7. Polymicrobial Interactions in the Lung
    JENNIFER MELINDA BOMBERGER; Fiscal Year: 2013
  8. South Carolina IDeA Network of Biomedical Research Excellence
    LUCIA AMELIA PIRISI-CREEK; Fiscal Year: 2013
  9. Epithelial Barrier Programs in Asthma and Allergic Disease
    Michael J Holtzman; Fiscal Year: 2013
  10. HORMONAL INFLUENCES ON AIRWAY DISEASE
    Raksha Jain; Fiscal Year: 2013

Detail Information

Research Grants30

  1. Improving Inhaled Drug Delivery with Self-dispersing Liquids
    STEPHEN GAROFF; Fiscal Year: 2013
    ..Knowledge gained from these studies could also be applied to the other inhaled medications and ultimately benefit the nearly 35 million Americans suffering from obstructive lung diseases. ..
  2. Cigarette Smoke and Susceptibility to Influenza Infection
    Terry L Noah; Fiscal Year: 2013
    ..abstract_text> ..
  3. Airway Inflammation and Airway Remodeling
    David H Broide; Fiscal Year: 2013
    ..An lOFM Core is also proposed as requested by the RFA. ..
  4. MECHANISMS AND MODULATION OF ACCELLULAR HbA TOXICITY
    Joel M Friedman; Fiscal Year: 2013
    ..Olson, leader);Core D, Chemical, Cellular, And Animal Toxicity Evaluations (FDA, Alayash leader) ..
  5. Primary Immune Deficiency Treatment Consortium
    Morton Cowan; Fiscal Year: 2013
    ..These studies will resolve critical questions concerning HCT for these disorders and form the basis for future prospective clinical trials. ..
  6. Novel approaches for vaccine design
    Michel C Nussenzweig; Fiscal Year: 2013
    ..abstract_text> ..
  7. Polymicrobial Interactions in the Lung
    JENNIFER MELINDA BOMBERGER; Fiscal Year: 2013
    ..aeruginosa reduces the ability of the lung to clear viral infections and, ultimately, identify new therapeutic approaches to control combined P. aeruginosa and respiratory virus infections. ..
  8. South Carolina IDeA Network of Biomedical Research Excellence
    LUCIA AMELIA PIRISI-CREEK; Fiscal Year: 2013
    ..We will intensify and focus our efforts to further build and support the pipeline for training, with particular attention to the recruitment and retention of minorities in biomedical science. ..
  9. Epithelial Barrier Programs in Asthma and Allergic Disease
    Michael J Holtzman; Fiscal Year: 2013
    ..abstract_text> ..
  10. HORMONAL INFLUENCES ON AIRWAY DISEASE
    Raksha Jain; Fiscal Year: 2013
    ..These findings could lead to novel therapeutic approaches involving inhaled hormone manipulation in patients with bronchiectasis and other airway diseases such as asthma and chronic obstructive pulmonary disease. ..
  11. Expanding Excellence in Developmental Biology in Oklahoma
    Linda F Thompson; Fiscal Year: 2013
    ..abstract_text> ..
  12. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013
    ..abstract_text> ..
  13. Chloride secretagogues for acquired CFTR dysfunction in chronic rhinosinusitis
    Bradford Alan Woodworth; Fiscal Year: 2013
    ....
  14. Evolving Microenvironments in Airway Inflammation
    George H Caughey; Fiscal Year: 2013
    ..End of Abstract) ..
  15. rAAV-directed gene therapy to the lung in cystic fibrosis ferret models
    John F Engelhardt; Fiscal Year: 2013
    ..This proposal will significantly enhance the field's ability to effectively develop therapeutic strategies for treatment of the CF lung, not only using rAAV vectors, but also other pharmacologic and gene-based therapies. ..
  16. Vascular Subphenotypes of Lung Disease
    Mark T Gladwin; Fiscal Year: 2013
    ..vascular disease Project 3: Pulmonary vascular-targeted NO therapeutic strategies Core A: Administrative core Core B: Pre-Clinical Models of PAH Core C: Translational Vascular Phenomics, Genomics and Epidemiology Core ..
  17. Spinal Cord Injury, Plasticity and Transplant Mediated Repair
    John D Houle; Fiscal Year: 2013
    ..This Program Project has direct relevance to the design and implementation of future treatment programs for acute and delayed intervention after SCI. ..
  18. PPG-Genetic and Signaling Mechanisms in the Central Regulation of Blood Pressure
    CURT DANIEL SIGMUND; Fiscal Year: 2013
    ..The findings will clarify important mechanisms, which may allow translation into improved treatment for cardiovascular and metabolic dysfunction in hypertension and obesity-hypertension. ..
  19. GENE AND PHARMACOLOGICAL THERAPIES FOR CYSTIC FIBROSIS
    William B Guggino; Fiscal Year: 2013
    ..Project IV will focus on the Biology of AAV. Finally, there are three cores, an Expression, a Vector Core, and an Administration Core. ..
  20. OPTIMIZE - CCC - Lead Application
    Bonnie W Ramsey; Fiscal Year: 2013
    ..Previously unstudied characteristics of the respiratory microbiome predictive of poor microbiologic and/or clinical response will be identified. This CCC lead application is submitted with a DCC application. ..
  21. Airway inflammation and HLA-G in asthma
    Steven R White; Fiscal Year: 2013
    ..abstract_text> ..