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IPF Overview With a Focus on Pathophysiology and Pathogenesis PowerPoint Presentation
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IPF Overview With a Focus on Pathophysiology and Pathogenesis

IPF Overview With a Focus on Pathophysiology and Pathogenesis

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IPF Overview With a Focus on Pathophysiology and Pathogenesis

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  1. IPF Overview With a Focus on Pathophysiology and Pathogenesis

  2. Objective Discuss evolving concepts in the pathophysiology and pathogenesis of IPF

  3. Evolving Classification of IPF Interstitial Lung Diseases UIP/IPF Sarcoidosis Hypersensitivity Pneumonitis DIP RB-ILD A heterogeneous group that included a number of diseases AIP 1970s 2002 NSIP Cellular Fibrotic COP Asbestosis LAM etc LIP Adapted from ATS/ERS Consensus Statement. Am J Resp Crit Care Med. 2002;165:277-304.

  4. Current Definition of IPF A distinct type of chronic fibrosing interstitial pneumonia of unknown cause, limited to the lungs, and associated with a surgical lung biopsy showing a histologic pattern of UIP ATS/ERS Consensus Statement. Am J Resp Crit Care Med. 2002;165:277-304. ATS/ERS Consensus Statement. Am J Resp Crit Care Med. 2000;161:646-664.

  5. Potential Risk Factors • Familial (genetic) • Smoking • Environmental factors (eg, occupational exposure to wood dust or metal dust) • Chronic aspiration associated with gastroesophageal reflux disease (GERD) • Infectious agents ATS/ERS Consensus Statement. Am J Resp Crit Care Med. 2000;161:646-664.

  6. US Demographics • Incidence: > 30,000 patients/year • Prevalence: > 80,000 current patients • Age of onset: 40 to 70 years • Two-thirds > 60 years old at presentation • Males > females • Caucasians > minorities ATS/ERS Consensus Statement. Am J Resp Crit Care Med. 2000;161:646-664. Weycker D, et al. Prevalence, Incidence, and Economic Costs of Idiopathic Pulmonary Fibrosis. Paper presented at: CHEST 2002, November 2-7, 2002; San Diego, California.

  7. Epidemiology of IPF Incidence Prevalence 120 300 100 250 Male Male Female 80 Female 200 60 150 40 100 20 50 0 0 45-54 55-64 65-74 75+ 45-54 55-64 65-74 75+ Estimated 31,000 New Patients per Year in the United States Estimated 83,000 CurrentPatients in the United States Weycker D, et al. Prevalence, Incidence, and Economic Costs of Idiopathic Pulmonary Fibrosis. Paper presented at: CHEST 2002, November 2-7, 2002; San Diego, California.

  8. Survival Curve for IIP Patients Grouped by Histologic Classification Time (years) 1.0 NSIP (n = 30) 0.9 0.8 0.7 0.6 Discordant UIP (n = 28) 0.5 Cumulative Proportion Surviving 0.4 0.3 Concordant UIP (n = 51) P <0.0003 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 Flaherty KR, et al. Am J Respir Crit Care Med. 2001;164:1722-1727.

  9. UIP: A Histologic Study of Biopsy and Explant Specimens • Areas resembling NSIP often present in UIP • If areas of NSIP and UIP are both present, UIPdetermines prognosis • Potential confounding histologic features may be present in UIP • Acute process superimposed on UIP • Diffuse alveolar damage and BOOP superimposed on UIP • Extensive honeycomb change may obscure diagnosis of UIP Katzenstein AA, et al. Am J Surg Pathol. 2002;26(12):1567-1577.

  10. UIP Gene Chip Data • Groups of genes significantly overexpressedin UIP • Muscle markers • Extracellular matrix, growth factors, and proteases • Cytokines, chemokines, and antioxidants • Complement, immunoglobulins, and amyloid Zuo F, et al. Proc Natl Acad Sci USA. 2002;99(9):6292-6297.

  11. Histopathological Patterns of IIPs LUNG INJURY AgeGenetic factorsEnvironmental factorsNature of injury – Etiologic agent – Recurrent vs single – Endothelial vs epithelial Histopathologic Pattern DIP RB-ILD LIP COP NSIP AIP UIP Inflammation Fibrosis Thannickal VJ, et al. Annu Rev Med. 2004;55:395-417.

  12. What Is the Natural History of UIP/IPF? UIP UIP UIP Natural History/Pathogenesis of Disease Beginning Intermediate End Stage Stage/Phase Slide courtesy of Robert Strieter, MD

  13. UIP End Stage A Potential Natural History of the Pathogenesis of NSIP  UIP NSIP NSIP-F Intermediate Beginning Stage/Phase Flaherty KR, et al. Am J Respir Crit Care Med. 2001;164:1722-1727. Slide courtesy of Robert Strieter, MD

  14. Progression of IPF:Acute Exacerbation vs Slow Decline Traditional View of UIP/IPF Progression Respiratory Function/Symptoms 50% FVC 1 2 3 4 Years FVC = forced vital capacity

  15. Progression of IPF:Acute Exacerbation vs Slow Decline Step Theory of UIP/IPF Progression Respiratory Function/Symptoms FVC 50% Acute exacerbation 1 2 3 4 0 Years

  16. Progression of Lung Fibrosis Injury Epithelial cells Capillary Slide courtesy of Paul Noble, MD

  17. Tissue Model of Lung Fibrosis Cell death Epithelial cells Growth factors and other products of epithelial cell Injury Capillary Myofibroblast Collagen Slide courtesy of Paul Noble, MD

  18. Pathology of IPF: Peripheral Accentuation of Disease Slide courtesy of Kevin Leslie, MD

  19. Pathology of IPF:Transition to Uninvolved Lung Present in the Biopsy Slide courtesy of Kevin Leslie, MD

  20. Pathology of UIP/IPF Slide courtesy of Kevin Leslie, MD

  21. Fibroblastic Focus in UIP Slide courtesy of Kevin Leslie, MD

  22. IPF: Potential Contributing Pathways GROWTH FACTOR ANGIOSTATIC CHEMOKINES DIRECT MARKERS OF FIBROSIS IMMUNOMODULATING CYTOKINES AND CHEMOKINES ANGIOGENIC FACTORS NEUTROPHIL CHEMOTAXIS/ACTIVATION ANTIMICROBIAL FACTORS Slide courtesy of Robert Strieter, MD