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Colorado Clinical Proteomics Program

Colorado Clinical Proteomics Program. 1. Pediatric Lung Disease 2. Hypothesis and Specific Aims 3. Colorado Clinical Proteomics Program - Organization - Setting - Cores - Networks - Special Features. Childhood. Adult Lung Disease. Morbidity Mortality. Lung Disease.

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Colorado Clinical Proteomics Program

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  1. Colorado Clinical Proteomics Program 1. Pediatric Lung Disease 2. Hypothesis and Specific Aims 3. Colorado Clinical Proteomics Program - Organization - Setting - Cores - Networks - Special Features Colorado Clinical Proteomics Program

  2. Childhood Adult Lung Disease Morbidity Mortality Lung Disease Protein Biomarkers - Assessment difficult - Non-invasive sampling - Small volume specimens Pediatric Lung Disease Asthma, Bronchopulmonary Dysplasia, Cystic Fibrosis, Pulmonary Artery Hypertension Colorado Clinical Proteomics Program

  3. Asthma Reversible Airway Obstruction Pediatric Asthma - 10-35% of all children - Quality of Life, School Attendance - Morbidity, Hospitalization 4/1000 - Mortality - Cost (Sennhauser et al, 2005; Engelsvold, Omyar, 2003; Myers, 2000) Colorado Clinical Proteomics Program

  4. Bronchopulmonary Dysplasia (BPD) - 0.2% to 1% newborns (10,000-40,000/yr) - 60% Readmission rate - Increasing rate of premature births - Surfactant - Decreased severity - No change in Incidence • BPD • Chronic Lung Disease • Preterm Infants • Mechanical Ventilation • All Lung Components (Wen et al, 2004) Colorado Clinical Proteomics Program

  5. Cystic Fibrosis (CF) - 17,000 Children - 20% Hospitalized - Progressive Loss Of Lung function - Median age of Death (25 years) - Cost • Cystic Fibrosis • Genetic • Failure of • Airway Defense (CF Foundation Patient Registry 2003, Bethesda, MD) Colorado Clinical Proteomics Program

  6. Pulmonary Arterial Hypertension (PAH) • PAH • CHD • Idiopathic • Developmental • Abnormalities • Mortality – 10 year 40% • Morbidity • Prolonged hospitalizations • 240 followed at Colorado (Yung et al, 2004) Colorado Clinical Proteomics Program

  7. Clinical Proteomics Potential • Asthma BPD CF PAH • Population screening Yes • Susceptibility • Staging • Rapid progression study study • Exacerbation • - Identification • - Susceptibility study • Response to tx study study • Toxicity with tx • Clin Trial stratification • Outcome Measures • Clues to Pathogenesis • Inflammation,Fibrosis Yes(?) Yes Yes Yes Colorado Clinical Proteomics Program

  8. Hypothesis and Specific Aims • Hypothesis: Development and Validation of Protein Bio- • Markers will lead to improved care in Pediatric Lung Disease • Aim 1. Establish a Clinical Proteomics Program in Pediatric • Lung Disease comprising five cores to develop and validate • panels of Protein Biomarkers • Aim 2. Address specific issues in Pediatric Lung Disease • through panels of protein biomarkers: • Asthma – frequent exacerbations, failure to respond to Tx • CF, BPD – identification of rapid progressors • PAH – failure to respond to Tx • Aim 3. Develop Educational Program in Clinical Proteomics • Aim 4. Develop a National Resource for NHLBI investig. Colorado Clinical Proteomics Program

  9. Colorado Clinical Proteomics Program – Organization NHLBI Clinical Proteomics Steering Committee Colorado Steering Committee - Heads of Core, M. Duncan, Proteomics Consultant. - Clinical Core – F. Accurso, MD (PI) - Laboratory Core – R. Harbeck, PhD - Data Management/Biostatistics – J. Murphy, PhD - Educational Core – R. Deterding, MD; L. Shroyer, PhD - Administrative Core – F. Accurso, MD Colorado Clinical Proteomics Program

  10. Colorado Clinical Proteomics Program – Setting Childrens Hospital Clinical, Lab, Admin 3 miles National Jewish Center Clinical, Lab, DMU/Biostats 6 blocks University of Colorado Veterans Administration Education, Biostats Colorado Clinical Proteomics Program

  11. Clinical Core Director: F. Accurso, MD Asthma: S. Szefler, MD, National Jewish - CAMP, ICAC BPD: S. Abman, MD; J. Kinsella, MD Children’s Hospital, University - NHLBI funded trial of nitric oxide in prevention of BPD PAH: S. Abman, MD; D. Ivy, MD, Children’s Hospital, Univ. - Local, Multicenter trials CF: F. Accurso, MD, Children’s Hospital, Univ. - CF Foundation Therapeutics Development Network Regulatory Compliance: HIPAA, Institutional Review Board Colorado Clinical Proteomics Program

  12. Specimen Collection Sample Processing Storage Analysis Validation Luminex Platform Laboratory Core Director: R. Harbeck, PhD IL-1-8-10, -12, -13, 15, GM-CSF, IFN, TNF, eotaxin, MCP-1, RANTES, MIP-1, VEG F Colorado Clinical Proteomics Program

  13. Data Management/Biostatistics Core Director: J. Murphy, PhD Phase 1Phase 2Phase 3Phase 4Phase 5 Exploratory Clinical Assay Retrospective Prospective Large Scale Studies Development/ Longitudinal Longitudinal Application Validation Validation Validation • Data Management: • - Implementation • - Regulatory Compliance • Biostatistics: J. Murphy; G. Zerbe, PhD. • - Statistics appropriate for each Phase (Pepe et al, 2001; Srinivas et al, 2002) Colorado Clinical Proteomics Program

  14. Education Core Co-Directors: R. Deterding, ,MD, L. Shroyer, PhD • Clinical Science Program, K30, med school curriculum • Local, National and Web Based Goals • Curriculum Design, Implementation, Evaluation, Dissemination • Trainees: Multidisciplinary backgrounds, all levels Year 1 Year 2 Year 3 Year 4 Curriculum Pilot Local Full Local Evaluate Local Development Start National National (ATS, ACCP) Start Web based Web based Evaluate National Colorado Clinical Proteomics Program

  15. Clinical Study Timeline: CF Colorado Clinical Proteomics Program

  16. Colorado Clinical Proteomics Program 1. Pediatric Lung Disease 2. Hypothesis and Specific Aims 3. Colorado Clinical Proteomics Program - Organization - Setting - Cores - Networks - Special Features Collaboration with M. Duncan, Proteomics, Randox Laboratories, Protein Arrays Colorado Clinical Proteomics Program

  17. Experience with Matrices Other than Plasma or Serum • Sputum (Sagel et al. 2001) • BAL (Khan et al. 1995) • Bronchial Brushing (Wooldridge et al, 2004) • Breath Condensate • Urine • - Proteomic Study of Urinary Biomarkers in CF • Exacerbation • - Collaboration with M. Duncan and S. Hunsucker Colorado Clinical Proteomics Program

  18. Protein Biomarker Timeline:Immunoreactive Trypsinogen (IRT) 1979 1991 1995 2004 Clinical Benefit (Farrell et al) Pilot CF Screening (Eliot et al) Validated (Hammond et al) CDC, CF Found. Endorse- ment Colorado Screening Program (n>1,000,000) We need to do better. Colorado Clinical Proteomics Program

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