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Am. J. Respir. Crit. Care Med., Volume 164, Number 6, September 2001, 1025-1032

Idiopathic Pulmonary Fibrosis
Relationship between Histopathologic Features and Mortality

TALMADGE E. KING JR., MARVIN I. SCHWARZ, KEVIN BROWN, JANET A. TOOZE, THOMAS V. COLBY, JAMES A. WALDRON JR., ANDREW FLINT, WILLIAM THURLBECK, and REUBEN M. CHERNIACK

Department of Medicine, San Francisco General Hospital, and the University of California, San Francisco, San Francisco, California; Department of Medicine, National Jewish Medical and Research Center, and the Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado; Departments of Pathology, Mayo Clinic, Scottsdale, Arizona; University of Arkansas, Little Rock, Arkansas; University of Michigan, Ann Arbor, Michigan; University of British Columbia, Vancouver, British Columbia, Canada

It is hypothesized that the extent and severity of fibrosis and cellularity found on lung biopsy determine the prognosis and response to therapy in idiopathic pulmonary fibrosis (IPF). The objective of this study was to determine which histopathologic features predict survival in IPF. We prospectively studied 87 patients with usual interstitial pneumonia (UIP) confirmed by surgical lung biopsy. Four pathologists independently graded the extent and severity of specific histopathologic features. We used Cox proportional-hazards models to assess the effect of histopathologic patterns on patients' survival. The effects of age, sex, and smoking were also included in the analysis. Sixty-three patients died during the 17-yr study period. Survival was longer in subjects with lesser degrees of granulation/connective tissue deposition (fibroblastic foci). The degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did not affect survival. A history of cigarette smoking, the level of dyspnea, and the degree of lung stiffness at presentation were also shown to be independent factors predicting survival. The extent of fibroblastic foci present on lung biopsy predicts survival in IPF. These findings support the hypothesis that the critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing epithelial damage and repair process associated with persistent fibroblastic proliferation. Controlling these processes, rather than stopping inflammation, appears most important in preventing progressive disease and the fatal outcome common in IPF.




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Y. Kitasato, T. Hoshino, M. Okamoto, S. Kato, Y. Koda, N. Nagata, M. Kinoshita, H. Koga, D.-Y. Yoon, H. Asao, et al.
Enhanced Expression of Interleukin-18 and its Receptor in Idiopathic Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., December 1, 2004; 31(6): 619 - 625.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
M. W. Wynes, S. K. Frankel, and D. W. H. Riches
IL-4-induced macrophage-derived IGF-I protects myofibroblasts from apoptosis following growth factor withdrawal
J. Leukoc. Biol., November 1, 2004; 76(5): 1019 - 1027.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. Clement and committee members
Task force on chronic interstitial lung disease in immunocompetent children
Eur. Respir. J., October 1, 2004; 24(4): 686 - 697.
[Abstract] [Full Text] [PDF]

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 RadiologyHome page
S. R. Desai, S. Veeraraghavan, D. M. Hansell, A. Nikolakopolou, N. S. L. Goh, A. G. Nicholson, T. V. Colby, C. P. Denton, C. M. Black, R. M. du Bois, et al.
CT Features of Lung Disease in Patients with Systemic Sclerosis: Comparison with Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia
Radiology, August 1, 2004; 232(2): 560 - 567.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
C. Jakubzick, E. S. Choi, K. J. Carpenter, S. L. Kunkel, H. Evanoff, F. J. Martinez, K. R. Flaherty, G. B. Toews, T. V. Colby, W. D. Travis, et al.
Human Pulmonary Fibroblasts Exhibit Altered Interleukin-4 and Interleukin-13 Receptor Subunit Expression in Idiopathic Interstitial Pneumonia
Am. J. Pathol., June 1, 2004; 164(6): 1989 - 2001.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
A. R. Hill, O. Fruchter, M. D. Eisner, P. G. Tsoutsou, K. I. Gourgoulianis, J. S. Vourlekis, L. Richeldi, G. Raghu, T. E. King Jr., and A. S. Teirstein
Interferon Gamma-1b for Pulmonary Fibrosis
N. Engl. J. Med., April 22, 2004; 350(17): 1794 - 1797.
[Full Text] [PDF]

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 ChestHome page
D. S. Zander
Idiopathic Interstitial Pneumonias and the Concept of the Trump Card
Chest, February 1, 2004; 125(2): 359 - 360.
[Full Text] [PDF]

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 ChestHome page
H. Monaghan, A. U. Wells, T. V. Colby, R. M. du Bois, D. M. Hansell, and A. G. Nicholson
Prognostic Implications of Histologic Patterns in Multiple Surgical Lung Biopsies From Patients With Idiopathic Interstitial Pneumonias
Chest, February 1, 2004; 125(2): 522 - 526.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
V. N. Lama, K. R. Flaherty, G. B. Toews, T. V. Colby, W. D. Travis, Q. Long, S. Murray, E. A. Kazerooni, B. H. Gross, J. P. Lynch III, et al.
Prognostic Value of Desaturation during a 6-Minute Walk Test in Idiopathic Interstitial Pneumonia
Am. J. Respir. Crit. Care Med., November 1, 2003; 168(9): 1084 - 1090.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
M. Chiyo, Y. Sekine, T. Iwata, K. Tatsumi, K. Yasufuku, A. Iyoda, M. Otsuji, S. Yoshida, K. Shibuya, T. Iizasa, et al.
Impact of interstitial lung disease on surgical morbidity and mortality for lung cancer: analyses of short-term and long-term outcomes
J. Thorac. Cardiovasc. Surg., October 1, 2003; 126(4): 1141 - 1146.
[Abstract] [Full Text] [PDF]

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 ChestHome page
D. W. Kamp
Idiopathic Pulmonary Fibrosis: The Inflammation Hypothesis Revisited
Chest, October 1, 2003; 124(4): 1187 - 1190.
[Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Cisneros-Lira, M. Gaxiola, C. Ramos, M. Selman, and A. Pardo
Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs
Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L949 - L956.
[Abstract] [Full Text] [PDF]

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 ChestHome page
A. F. Shorr, D. B. Davies, and S. D. Nathan
Predicting Mortality in Patients With Sarcoidosis Awaiting Lung Transplantation
Chest, September 1, 2003; 124(3): 922 - 928.
[Abstract] [Full Text] [PDF]

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 ChestHome page
R. M. Ross
The Clinical Diagnosis of Asbestosis in This Century Requires More Than a Chest Radiograph
Chest, September 1, 2003; 124(3): 1120 - 1128.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
N. Kaminski, J. A. Belperio, P. B. Bitterman, L. Chen, S. W. Chensue, A. M.K. Choi, S. Dacic, J. H. Dauber, R. M. du Bois, J. J. Enghild, et al.
Idiopathic Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): S1 - 105.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
H. R. Collard, T. E. King Jr., B. B. Bartelson, J. S. Vourlekis, M. I. Schwarz, and K. K. Brown
Changes in Clinical and Physiologic Variables Predict Survival in Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 538 - 542.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
K. R. Flaherty, J. A. Mumford, S. Murray, E. A. Kazerooni, B. H. Gross, T. V. Colby, W. D. Travis, A. Flint, G. B. Toews, J. P. Lynch III, et al.
Prognostic Implications of Physiologic and Radiographic Changes in Idiopathic Interstitial Pneumonia
Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 543 - 548.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. I. Latsi, R. M. du Bois, A. G. Nicholson, T. V. Colby, D. Bisirtzoglou, A. Nikolakopoulou, S. Veeraraghavan, D. M. Hansell, and A. U. Wells
Fibrotic Idiopathic Interstitial Pneumonia: The Prognostic Value of Longitudinal Functional Trends
Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 531 - 537.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
G. Thabut, H. Mal, Y. Castier, O. Groussard, O. Brugiere, R. Marrash-Chahla, G. Leseche, and M. Fournier
Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis
J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 469 - 475.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
K. R. Flaherty, T. V. Colby, W. D. Travis, G. B. Toews, J. Mumford, S. Murray, V. J. Thannickal, E. A. Kazerooni, B. H. Gross, J. P. Lynch III, et al.
Fibroblastic Foci in Usual Interstitial Pneumonia: Idiopathic versus Collagen Vascular Disease
Am. J. Respir. Crit. Care Med., May 15, 2003; 167(10): 1410 - 1415.
[Abstract] [Full Text] [PDF]

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 Arch Intern MedHome page
H. R. Collard and T. E. King Jr
Demystifying Idiopathic Interstitial Pneumonia
Arch Intern Med, January 13, 2003; 163(1): 17 - 29.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
M. N. Gong and E. J. Mark
Case 40-2002 - A 56-Year-Old Man with Rapidly Worsening Dyspnea
N. Engl. J. Med., December 26, 2002; 347(26): 2149 - 2157.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Compliance (COMmunicate PLease wIth Less Abbreviations, Noun Clusters, and Exclusiveness)
Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): 1534 - 1536.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
A. G. Nicholson, L. G. Fulford, T. V. Colby, R. M. du Bois, D. M. Hansell, and A. U. Wells
The Relationship between Individual Histologic Features and Disease Progression in Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 173 - 177.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
J. S. Hagood, A. Mangalwadi, B. Guo, M. W. MacEwen, L. Salazar, and G. M. Fuller
Concordant and Discordant Interleukin-1-Mediated Signaling in Lung Fibroblast Thy-1 Subpopulations
Am. J. Respir. Cell Mol. Biol., June 1, 2002; 26(6): 702 - 708.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. R. Khoshnevis, T. E. King Jr., and J. Tooze
Histopathology and prediction of survival in usual interstitial pneumonia
Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1451 - 1452.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. Gauldie
Inflammatory Mechanisms Are a Minor Component of the Pathogenesis of Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1205 - 1206.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
R. M. Strieter
Inflammatory Mechanisms Are Not a Minor Component of the Pathogenesis of Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1206 - 1207.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. J. TOBIN
Tuberculosis, Lung Infections, Interstitial Lung Disease, and Socioeconomic Issues in AJRCCM 2001
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 631 - 641.
[Full Text] [PDF]


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