Download PDF
Semin Respir Crit Care Med 2001; 22(4): 357-386
DOI: 10.1055/s-2001-17381
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Usual Interstitial Pneumonia

Joseph P. Lynch, III1 , Mark Wurfel3 , Kevin Flaherty1 , Eric White1 , Fernando Martinez1 , William Travis2 , Ganesh Raghu3
  • 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
  • 2Armed Forces Institute of Pathology, Washington, D.C
  • 3Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington
Further Information

Publication History

Publication Date:
26 September 2001 (online)

    Permissions and Reprints

ABSTRACT

Usual interstitial pneumonia (UIP) is a distinct histological lesion observed in idiopathic pulmonary fibrosis (IPF), but can be found in other etiologies. The diagnosis of UIP can be established by surgical lung biopsy or by high resolution thin section computed tomographic scans (provided the radiographic features are classical). Historically, patients labeled as ``IPF'' encompassed a group of disorders including UIP as well as other idiopathic interstitial pneumonias, which differ from UIP in prognosis and responsiveness to therapy. Current recommendations from international consensus statements restrict the term IPF to patients with idiopathic UIP. The inciting cause(s) and pathogenesis of UIP have not been elucidated, but alveolar epithelial cell injury and dysregulation or altered phenotypic expression of fibroblasts are key elements. Inflammatory cells may play minor roles in initiating or propagating the fibrotic process. The prognosis of UIP is poor. Mean survival following diagnosis approximates 3 years. Current therapies are of unproven value. Corticosteroids or immunosuppressive agents have been most often used, but data affirming benefit are lacking. Single-lung transplantation is a viable option for patients failing medical therapy. Novel therapeutic strategies based upon inhibiting fibroproliferation or enhancing alveolar reepithelialization are desperately needed. In this article, we discuss diagnostic criteria for UIP (both histopathological and radiographic), natural history and clinical course, and therapeutic approaches (both current and future).

KEYWORD

Usual interstitial pneumonia (UIP) - idiopathic pulmonary fibrosis (IPF) - cryptogenic fibrosing alveolitis (CFA) - fibroblast - fibroblastic foci - honeycombing

REFERENCES

  • 1 Katzenstein A LA, Myers J L. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.  Am J Respir Crit Care Med . 1998;  157 1301-1315
    CrossrefPubMedGoogle Scholar
  • 2 American Thoracic Society, European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International Consensus Statement.  Am J Respir Crit Care Med . 2000;  161 646-664
    Google Scholar
  • 3 British Thoracic Society. The diagnosis, assessment, and treatment of diffuse parenchymal lung disease in adults: British thoracic society recommendations.  Thorax . 1999;  54 S1-S30
    PubMedGoogle Scholar
  • 4 Lynch III J P, Orens J, Kazerooni  E A. Collagen vascular diseases. In: Sperber, M, ed. Diffuse Lung Diseases: A Comprehensive Clinical-Radiological Overview London: Springer-Verlag 1999: 325-355
    Google Scholar
  • 5 Winterbauer R H, Hammar S P, Hallman K O. Diffuse interstitial pneumonitis: clinicopathologic correlations in 20 patients treated with prednisone/azathioprine.  Am J Med . 1978;  65 661-672
    CrossrefPubMedGoogle Scholar
  • 6 Carrington C B, Gaensler E A, Coutu R E. Natural history and treated course of usual and desquamative interstitial pneumonia.  N Engl J Med . 1978;  298 801-809
    CrossrefPubMedGoogle Scholar
  • 7 Ryu J H, Colby T V, Hartman T E. Idiopathic pulmonary fibrosis: current concepts.  Mayo Clin Proc . 1998;  73 1085-1101
    PubMedGoogle Scholar
  • 8 Bjoraker J A, Ryu J H, Edwin M K. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1998;  157 199-203
    CrossrefPubMedGoogle Scholar
  • 9 Daniil Z D, Gilchrist F C, Nicholson A G. A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis.  Am J Respir Crit Care Med . 1999;  160 899-905
    CrossrefPubMedGoogle Scholar
  • 10 Travis W D, Matsui K, Moss J. Idiopathic nonspecific intersititial pneumonia: prognostic signficance of cellular and fibrosing patterns.  Am J Surg Path . 2000;  24 19-33
    CrossrefPubMedGoogle Scholar
  • 11 Nicholson A G, Colby T V, du Bois M R. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis.  Am J Respir Crit Care Med . 2000;  162 2213-2217
    CrossrefPubMedGoogle Scholar
  • 12 Hartman T E, Primac S L, Kang E Y. Desquamative interstitial pneumonia: thin section CT findings in 22 patients.  Radiology . 1993;  187 787-790
    CrossrefPubMedGoogle Scholar
  • 13 Hartman T E, Primac S L, Kang E Y. Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia: assessment with serial CT.  Chest . 1996;  110 378-382
    CrossrefPubMedGoogle Scholar
  • 14 Yousem S A, Colby T V, Gaensler E A. Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia.  Mayo Clin Proc . 1989;  64 1373-1380
    CrossrefPubMedGoogle Scholar
  • 15 Myers J L, Veal Jr F C, Shin M S. Respiratory bronchiolitis causing interstitial lung disease: clinicopathologic study of six cases.  Am Rev Respir Dis . 1987;  135 880-884
    CrossrefPubMedGoogle Scholar
  • 16 Katzenstein A LA, Fiorelli R F. Nonspecific interstitial pneumonia/fibrosis: histologic features and clinical significance.  Am J Surg Pathol . 1994;  18 136-147
    CrossrefPubMedGoogle Scholar
  • 17 Nagai S, Kitaichi M, Itoh H. Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP.  Eur Respir J . 1998;  12 1010-1019
    CrossrefPubMedGoogle Scholar
  • 18 Katzenstein A LA, Myers J L, Mazur M T. Acute interstitial pneumonia: a clinicopathologic, ultrastructural, and cell kinetic study.  Am J Surg Pathol . 1986;  10 256-267
    CrossrefPubMedGoogle Scholar
  • 19 Vourlekis J S, Brown K K, Cool C D. Acute interstitial pneumonitis: case series and review of the literature.  Medicine . 2000;  79 369-378
    PubMedGoogle Scholar
  • 20 Bouros D, Nicholson A G, Polychronopoulos V. Acute interstitial pneumonia.  Eur Respir J . 2000;  15 412-418
    CrossrefPubMedGoogle Scholar
  • 21 Nicholson A G, Wotherspoon A C, Diss T C. Reactive pulmonary lymphoid disorders.  Histopathol . 1995;  26 405-412
    PubMedGoogle Scholar
  • 22 Travis W D, Fox C H, Devaney K O. Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.  Hum Pathol . 1992;  23 529-541
    CrossrefPubMedGoogle Scholar
  • 23 Koss M N, Hochholzer L, Langloss J M. Lymphoid interstitial pneumonia: clinicopathological and immunopathological findings in 18 cases.  Pathology . 1987;  19 178-185
    CrossrefPubMedGoogle Scholar
  • 24 Koss M N. Pulmonary lymphoid disorders.  Semin Diagn Pathol . 1995;  12 158-171
    PubMedGoogle Scholar
  • 25 Lazor R, Vandevenne A, Pelletier A. Cryptogenic organizing pneumonia: characteristics of relapses in a series of 48 patients.  Am J Respir Crit Care Med . 2000;  162 571-577
    CrossrefPubMedGoogle Scholar
  • 26 Alasaly K, Muller N L, Ostrow D. Cryptogenic organizing pneumonia: a report of 25 cases and a review of the literature.  Medicine . 1995;  74 201-211
    CrossrefPubMedGoogle Scholar
  • 27 Cherniak R M, Colby T V, Flint A. Correlation of structure and function in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1995;  151 1180-1188
    PubMedGoogle Scholar
  • 28 Cherniak R M, Colby T V, Flint A. Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis. The BAL cooperative group steering committee.  Am Rev Respir Dis . 1991;  144 892-900
    PubMedGoogle Scholar
  • 29 Hyde D M, King Jr E T, McDermott T. Idiopathic pulmonary fibrosis: quantitative assessment of lung pathology: comparison of a semiquantitative and morphometric histopathologic scoring system.  Am Rev Respir Dis . 1992;  146 1042-1047
    PubMedGoogle Scholar
  • 30 Hunninghake G W, Zimmerman M B, Schwartz D A. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 2001;  164 193-196
    CrossrefPubMedGoogle Scholar
  • 31 Kuhn C, McDonald J A. The roles of the myofibroblast in idiopathic pulmonary fibrosis: ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis.  Am J Pathol . 1991;  138 1257-1265
    PubMedGoogle Scholar
  • 32 Kuhn III C, Boldt J, King Jr E T. An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis.  Am Rev Respir Dis . 1989;  140 1693-1703
    PubMedGoogle Scholar
  • 33 Bensadoun E S, Burke A K, Hogg J C. Proteoglycan deposition in pulmonary fibrosis.  Am J Respir Crit Care Med . 1996;  154 1819-1828
    PubMedGoogle Scholar
  • 34 Fukuda Y, Basset F, Ferrans V J. Significance of early intraalveolar fibrotic lesions and integrin expression in lung biopsy specimens from patients with idiopathic pulmonary fibrosis.  Hum Pathol . 1995;  26 53-61
    CrossrefPubMedGoogle Scholar
  • 35 Wallace W A, Howie S E, Lamb D. Tenascin immunoreactivity in cryptogenic fibrosing alveolitis.  J Pathol . 1995;  175 415-420
    PubMedGoogle Scholar
  • 36 Corrin B. Pathology of interstitial lung disease.  Semin Respir Crit Care Med . 1994;  15 61-76
    PubMedGoogle Scholar
  • 37 Moon J, du Bois M R, Colby T V. Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease.  Thorax . 1999;  54 1009-1014
    CrossrefPubMedGoogle Scholar
  • 38 Flaherty K R, Travis W D, Colby T V. Histopathological variability in idiopathic interstitial pneumonia: clinical implications.  Am J Respir Crit Care Med In press.
    PubMedGoogle Scholar
  • 39 Flaherty K R, Toews G B, Travis W D. Clinical significance of histopathological classification of idiopathic interstitial pneumonia.  Eur Respir J In press.
    PubMedGoogle Scholar
  • 40 Katzenstein A L, Myers J L. Nonspecific interstitial pneumonia and the other idiopathic interstitial pneumonias: classification and diagnostic criteria.  Am J Surg Pathol . 2000;  24 1-3
    CrossrefPubMedGoogle Scholar
  • 41 Raghu G, Mageto Y N, Lockhart D. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: a prospective study.  Chest . 1999;  116 1168-1174
    CrossrefPubMedGoogle Scholar
  • 42 Johnston I D, Gomm S A, Kalra S. The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.  Eur Respir J . 1993;  6 891-893
    PubMedGoogle Scholar
  • 43 Johnston I DA, Prescott B J, Chalmers J C. British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management.  Thorax . 1997;  2 38-44
    PubMedGoogle Scholar
  • 44 Mapel D W, Samet J M, Coultas D B. Corticosteroids and the treatment of idiopathic pulmonary fibrosis: past, present, and future.  Chest . 1996;  110 1058-1067
    PubMedGoogle Scholar
  • 45 Raghu G. Interstitial lung disease: a diagnostic approach: are CT scan and lung biopsy indicated for every patient?.  Am J Respir Crit Care Med . 1995;  151 909-914
    CrossrefPubMedGoogle Scholar
  • 46 Coultas D B, Zumwalt R E, Black W C. The epidemiology of interstitial lung diseases.  Am J Respir Crit Care Med . 1994;  150 967-972
    CrossrefPubMedGoogle Scholar
  • 47 Douglas W W, Ryu J H, Schroeder D R. Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone, or no therapy on survival.  Am J Respir Crit Care Med . 2000;  161 1172-1178
    CrossrefPubMedGoogle Scholar
  • 48 Utz J P, Ryu J H, Douglas W W. High short-term mortality following lung biopsy for usual interstitial pneumonia.  Eur Respir J . 2001;  17 175-179
    CrossrefPubMedGoogle Scholar
  • 49 Harris R J, Kavuru M S, Rice T W. The diagnostic and therapeutic utility of thoracoscopy: a review.  Chest . 1996;  108 828-841
    PubMedGoogle Scholar
  • 50 Hazelrigg S R, Nunchuck S K, LoCicero III J. Video assisted thoracic surgery study group data.  Ann Thorac Surg . 1993;  56 1039-1044
    PubMedGoogle Scholar
  • 51 Allen M S, Deschamps C, Jones D M. Video-assisted thoracic surgical procedures: the Mayo experience.  Mayo Clin Proc . 1996;  71 351-359
    PubMedGoogle Scholar
  • 52 Wells A. Clinical usefulness of high resolution computed tomography in cryptogenic fibrosing alveolitis.  Thorax . 1998;  53 1080-1087
    PubMedGoogle Scholar
  • 53 Gay S E, Kazerooni E A, Toews G B. Idiopathic pulmonary fibrosis: predicting response to therapy and survival.  Am J Respir Crit Care Med . 1998;  157 1063-1072
    CrossrefPubMedGoogle Scholar
  • 54 Wells A U, Hansell D M, Rubens M B. The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis.  Am Rev Respir Dis . 1993;  148 1076-1082
    CrossrefPubMedGoogle Scholar
  • 55 Nishimura K, Kitaichi M, Izumi T. Usual interstitial pneumonia: histologic correlation with high resolution CT.  Radiology . 1992;  182 337-342
    CrossrefPubMedGoogle Scholar
  • 56 Turner-Warwick M, Burrows B, Johnson A. Cryptogenic fibrosing alveolitis: response to corticosteroid treatment and its effect on survival.  Thorax . 1980;  35 593-599
    CrossrefPubMedGoogle Scholar
  • 57 Cottin V, Donsbeck A V, Revel D. Nonspecific interstitial pneumonia: individualization of a clinicopathologic entity in a series of 12 patients.  Am J Respir Crit Care Med . 1998;  158 1286-1293
    CrossrefPubMedGoogle Scholar
  • 58 Lynch P J, Toews G B. Idiopathic pulmonary fibrosis. In: Fishman A, ed. Textbook of Pulmonary Diseases and Disorders 3rd ed. New York: McGraw-Hill 1997: 1193-1210
    Google Scholar
  • 59 Doherty M J, Mister R, Pearson M G. Capsaicin induced cough in cryptogenic fibrosing alveolitis.  Thorax . 2000;  55 1028-1032
    CrossrefPubMedGoogle Scholar
  • 60 Lalloo U G, Lim S, du Bois M R. Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease.  Eur Respir J . 1998;  11 702-705
    PubMedGoogle Scholar
  • 61 Panos R J, Mortenson R L, Niccoli S A. Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment.  Am J Med . 1990;  88 396-404
    CrossrefPubMedGoogle Scholar
  • 62 Takahashi H, Fujishima T, Koba H. Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent.  Am J Respir Crit Care Med . 2000;  162 1109-1114
    CrossrefPubMedGoogle Scholar
  • 63 Watters L C, Schwarz M I, Cherniack R M. Idiopathic pulmonary fibrosis: pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.  Am Rev Respir Dis . 1987;  135 696-704
    PubMedGoogle Scholar
  • 64 Tukiainen P, Taskinen E, Holsti P. Prognosis of cryptogenic fibrosing alveolitis.  Thorax . 1983;  38 349-355
    CrossrefPubMedGoogle Scholar
  • 65 Hubbard R, Johnston I, Britton J. Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study.  Chest . 1998;  113 396-400
    CrossrefPubMedGoogle Scholar
  • 66 Erbes R, Schaberg T, Loddenkemper R. Lung function tests in patients with idiopathic pulmonary fibrosis: are they helpful for predicting outcome?.  Chest . 1997;  111 51-57
    CrossrefPubMedGoogle Scholar
  • 67 Lee J S, Ahn J M, Kim Y M. Fibrosing alveolitis: prognostic implication of ground-glass attenuation at high resolution CT.  Radiology . 1992;  184 451-454
    PubMedGoogle Scholar
  • 68 Nagai S, Kitaichi M, Hamada K. Hospital-based historical cohort study of 234 histologically proven Japanese patients with IPF.  Sarcoidosis Vasc Diffuse Lung Dis . 1999;  16 209-214
    PubMedGoogle Scholar
  • 69 Johnston I, Britton J, Kinnear W. Rising mortality from cryptogenic fibrosing alveolitis.  BMJ . 1990;  301 1017-1021
    PubMedGoogle Scholar
  • 70 U.S. Department of Health and Human Services. Vital and Health Statistics: National Hospital Discharge Survey, Annual Summary 1988 Hyattsville, MD: DHHS; 1991
  • 71 Johnston I D, Bleasdale C, Hind C R. Accuracy of diagnostic coding of hospital admissions for cryptogenic fibrosing alveolitis.  Thorax . 1991;  46 589-591
    PubMedGoogle Scholar
  • 72 Coultas D B, Hughes M P. Accuracy of mortality data for interstitial lung diseases in New Mexico, USA.  Thorax . 1996;  51 717-720
    PubMedGoogle Scholar
  • 73 Harris J M, Cullinan P, McDonald J C. Occupational distribution and geographic clustering of deaths certified to be cryptogenic fibrosing alveolitis in England and Wales.  Chest . 2001;  119 428-433
    CrossrefPubMedGoogle Scholar
  • 74 Scott J, Johnston I, Britton J. What causes cryptogenic fibrosing alveolitis?.  <~>A case control study of environmental exposure to dust. BMJ . 1990;  301 1015-1017
    PubMedGoogle Scholar
  • 75 Hubbard R, Johnston I, Coultas D B. Mortality rates from cryptogenic fibrosing alveolitis in seven countries.  Thorax . 1996;  51 711-716
    CrossrefPubMedGoogle Scholar
  • 76 Iawai K, Mori T, Yamada N. Idiopathic pulmonary fibrosis: epidemiologic approaches to occupational exposure.  Am J Respir Crit Care Med . 1994;  150 670-675
    CrossrefPubMedGoogle Scholar
  • 77 Doherty M J, Pearson M G, O'Grady E A. Cryptogenic fibrosing alveolitis with preserved lung volumes.  Thorax . 1997;  52 998-1002
    CrossrefPubMedGoogle Scholar
  • 78 Mannino D M, Etzel R A, Parrish R G. Pulmonary fibrosis deaths in the United States, 1979-1991; an analysis of multiple-cause mortality data.  Am J Respir Crit Care Med . 1996;  153 1548-1552
    CrossrefPubMedGoogle Scholar
  • 79 Hilman B C. Evaluation of interstitial lung disease in children.  Clin Pulm Med . 2001;  8 70-77
    PubMedGoogle Scholar
  • 80 Fan L L, Kozinetz C A. Factors influencing survival in children with chronic interstitial lung disease.  Am J Respir Crit Care Med . 1997;  156 939-942
    PubMedGoogle Scholar
  • 81 Lynch D A, Hay T C, Newell J D. Pediatric diffuse lung disease: diagnosis and classification by high resolution CT.  Radiology . 1997;  198 205P
    PubMedGoogle Scholar
  • 82 Osika E, Muller M H, Boccon-Gibod L. Idiopathic pulmonary fibrosis in infants.  Pediatr Pulmonol . 1997;  23 49-54
    PubMedGoogle Scholar
  • 83 Schwartz D A, Helmers R A, Dayton C S. Determinants of bronchoalveolar lavage cellularity in idiopathic pulmonary fibrosis.  J Appl Physiol . 1991;  71 1688-1693
    PubMedGoogle Scholar
  • 84 Baumgartner K B, Samet J M, Stidley C A. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1997;  155 242-248
    CrossrefPubMedGoogle Scholar
  • 85 Schwartz D A, Helmers R A, Galvin J R. Determinants of survival in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1994;  149 450-454
    CrossrefPubMedGoogle Scholar
  • 86 Billings C G, Howard P. Hypothesis: exposure to solvents may cause fibrosing alveolitis.  Eur Respir J . 1994;  7 1172-1176
    PubMedGoogle Scholar
  • 87 Mapel D W, Coultas D B. The environmental epidemiology of idiopathic interstitial lung disease including sarcoidosis.  Semin Respir Crit Care Med . 1999;  20 521
    PubMedGoogle Scholar
  • 88 Abraham J L, Hertzberg M A. Inorganic particulates associated with desquamative interstitial pneumonia.  Chest . 1981;  80 67-70
    PubMedGoogle Scholar
  • 89 Monso E, Tura J M, Marsal M. Mineralogical microanalysis of idiopathic pulmonary fibrosis.  Arch Environ Health . 1990;  45 185-188
    PubMedGoogle Scholar
  • 90 Gaensler E A, Jederlinic P J, Churg A. Idiopathic pulmonary fibrosis in asbestos-exposed workers.  Am Rev Respir Dis . 1991;  144 689-696
    PubMedGoogle Scholar
  • 91 Tobin R W, Pope C E, Pellegrini C A. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1998;  158 1804-1808
    PubMedGoogle Scholar
  • 92 Turner-Warwick M, Haslam P L. The value of serial bronchoalveolar lavages in assessing the clinical progress of patients with cryptogenic fibrosing alveolitis.  Am Rev Respir Dis . 1987;  135 26-34
    PubMedGoogle Scholar
  • 93 Perez-Padilla R, Salas J, Chapela R. Mortality in Mexican patients with chronic pigeon breeder's lung compared with those with usual interstitial pneumonia.  Am Rev Respir Dis . 1993;  148 49-53
    PubMedGoogle Scholar
  • 94 Smith C, Feldman C, Levy H. Cryptogenic fibrosing alveolitis: a study of an indigenous African population.  Respiration . 1990;  57 364-371
    PubMedGoogle Scholar
  • 95 Raghu G, Hert R. Interstitial lung diseases: genetic predisposition and inherited interstitial lung diseases.  Sem Respir Med . 1993;  14 323-332
    PubMedGoogle Scholar
  • 96 Marshall R P, Puddicombe A, Cookson W O. Adult familial cryptogenic fibrosing alveolitis in the United Kingdom.  Thorax . 2000;  55 143-146
    CrossrefPubMedGoogle Scholar
  • 97 Bitterman P B, Rennard S I, Keogh B A. Familial idiopathic pulmonary fibrosis: evidence of lung inflammation in unaffected family members.  N Engl J Med . 1986;  314 1343-1347
    CrossrefPubMedGoogle Scholar
  • 98 Marshall R P, McAnulty R J, Laurent G J. The pathogenesis of pulmonary fibrosis: is there a fibrosis gene?.  Int J Biochem Cell Biol . 1997;  29 107-120
    CrossrefPubMedGoogle Scholar
  • 99 Raghu G, Jarvik G, Lurton J. Genetic study of idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1996;  153 A405
    PubMedGoogle Scholar
  • 100 Musk A W, Zilko P J, Manners P. Genetic studies in familial fibrosing alveolitis: possible linkage with immunoglobulin allotypes (Gm).  Chest . 1986;  89 206-210
    CrossrefPubMedGoogle Scholar
  • 101 Hubbard R, Baoku Y, Kalsheker N. Alpha1-antitrypsin phenotypes in patients with cryptogenic fibrosing alveolitis: a case-control study.  Eur Respir J . 1997;  10 2881-2883
    CrossrefPubMedGoogle Scholar
  • 102 Whyte M, Hubbard R, Meliconi R. Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms.  Am J Respir Crit Care Med . 2000;  162 755-758
    CrossrefPubMedGoogle Scholar
  • 103 Hanson D, Winterbauer R H, Kirtland S H. Changes in pulmonary function test results after 1 year of therapy as predictors of survival in patients with idiopathic pulmonary fibrosis.  Chest . 1995;  108 305-310
    PubMedGoogle Scholar
  • 104 Flaherty K R, Martinez F J. The role of pulmonary function testing in pulmonary fibrosis.  Curr Opin Pulm Med . 2000;  6 404-410
    CrossrefPubMedGoogle Scholar
  • 105 Wells A U, King A D, Rubens M B. Lone cryptogenic fibrosing alveolitis: a functional-morphologic correlation based on extent of disease on thin-section computed tomography.  Am J Respir Crit Care Med . 1997;  155 1367-1375
    CrossrefPubMedGoogle Scholar
  • 106 Robertson H T. Clinical application of pulmonary function and exercise tests in the management of patients with interstitial lung disease.  Sem Respir Crit Care Med . 1994;  15 1-9
    PubMedGoogle Scholar
  • 107 Risk C, Epler G R, Gaensler E A. Exercise alveolar-arterial oxygen pressure difference in interstitial lung disease.  Chest . 1984;  85 69-74
    PubMedGoogle Scholar
  • 108 Dunn T L, Watters L C, Hendrix C. Gas exchange at a given degree of volume restriction is different in sarcoidosis and idiopathic pulmonary fibrosis.  Am J Med . 1988;  85 221-224
    CrossrefPubMedGoogle Scholar
  • 109 Epler G R, McLoud T C, Gaensler E A. Normal chest roentgenograms in chronic diffuse infiltrative lung disease.  N Engl J Med . 1978;  298 934-939
    CrossrefPubMedGoogle Scholar
  • 110 Orens J B, Kazerooni E A, Martinez F J. The sensitivity of high resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsy: a prospective study.  Chest . 1995;  108 109-115
    PubMedGoogle Scholar
  • 111 Hanley M E, King Jr E T, Schwarz M I. The impact of smoking on mechanical properties of the lungs in idiopathic pulmonary fibrosis and sarcoidosis.  Am Rev Respir Dis . 1991;  144 1102-1106
    CrossrefPubMedGoogle Scholar
  • 112 Fulmer J D, Roberts W C, von Gael R E. Morphologic-physiologic correlates of the severity of fibrosis and degree of cellularity in idiopathic pulmonary fibrosis.  J Clin Invest . 1979;  63 65-76
    PubMedGoogle Scholar
  • 113 Xaubet A, Agusti C, Luburich P. Pulmonary function tests and CT scan in the management of idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1998;  158 431-436
    CrossrefPubMedGoogle Scholar
  • 114 Bjoraker J A, Ryu J H, Edwin M K. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1998;  157 199-203
    CrossrefPubMedGoogle Scholar
  • 115 Chinet T, Jaubert F, Dusser D. Effects of inflammation and fibrosis on pulmonary function in diffuse lung fibrosis.  Thorax . 1990;  45 675-678
    PubMedGoogle Scholar
  • 116 Harris-Eze A O, Sridhar G, Clemens R E. Oxygen improves maximal exercise performance in interstitial lung disease.  Am J Respir Crit Care Med . 1994;  150 1616-1622
    CrossrefPubMedGoogle Scholar
  • 117 Agusti C, Xaubet A, Agusti A GN. Clinical and functional assessment of patients with idiopathic pulmonary fibrosis: results of a 3-year follow-up.  Eur Respir J . 1994;  7 643-650
    CrossrefPubMedGoogle Scholar
  • 118 Brantly M, Avila N A, Shotelersuk V. Pulmonary function and high resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansk-Pudlak Syndrome, due to mutations in HPS-1.  Chest . 2000;  117 129-136
    CrossrefPubMedGoogle Scholar
  • 119 Rudd R M, Haslam P L, Turner-Warwick M. Cryptogenic fibrosing alveolitis: relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis.  Am Rev Respir Dis . 1981;  124 1-8
    PubMedGoogle Scholar
  • 120 Jezek V, Fucik J, Michaljanic A. The prognostic significance of functional tests in kryptogenic fibrosing alveolitis.  Bull Eur Physiolpathol Respir . 1980;  16 711-720
    PubMedGoogle Scholar
  • 121 Johnson M A, Kwan S, Snell N J. Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.  Thorax . 1989;  44 280-288
    CrossrefPubMedGoogle Scholar
  • 122 Kangalee K M, Abboud R T. Interlaboratory and intralaboratory variability in pulmonary function testing: a 13-year study using a normal biologic control.  Chest . 1992;  101 88-92
    PubMedGoogle Scholar
  • 123 Crapo R O. Carbon monoxide diffusing capacity (transfer factor).  Sem Respir Crit Care Med . 1998;  19 335-347
    PubMedGoogle Scholar
  • 124 European Respiratory Society. Standardized lung function testing: official statement of the European Respiratory Society.  Eur Respir J . 1993 (suppl 16);  6 (1-100)
    PubMedGoogle Scholar
  • 125 Watters L C, King T E, Cherniack R M. Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis.  Am Rev Respir Dis . 1986;  133 104-109
    PubMedGoogle Scholar
  • 126 Marciniuk D D, Watts R E, Gallagher C G. Reproducibility of incremental maximal cycle ergometer testing in patients with restrictive lung disease.  Thorax . 1993;  48 894-898
    CrossrefPubMedGoogle Scholar
  • 127 Douglas W W, Ryu J H, Swensen S J. Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis: a randomized prospective study.  Am J Respir Crit Care Med . 1998;  158 220-225
    CrossrefPubMedGoogle Scholar
  • 128 Raghu G, Depaso W J, Cain K. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.  Am Rev Respir Dis . 1991;  144 291-296
    CrossrefPubMedGoogle Scholar
  • 129 Turner-Warwick M, Burrows B, Johnson A. Cryptogenic fibrosing alveolitis: response to corticosteroid therapy and its effect on survival.  Thorax . 1980;  35 593-599
    CrossrefPubMedGoogle Scholar
  • 130 Johnson S. Rare diseases. 1. Lymphangioleiomyomatosis: clinical features, management and basic mechanisms.  Thorax . 1999;  54 254-264
    PubMedGoogle Scholar
  • 131 Flaherty K R, Toews G B, Lynch III P J. Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival.  Am J Med . 2001;  110 278-282
    CrossrefPubMedGoogle Scholar
  • 132 Sciurba F C, Slivka W A. Six-minute walk testing.  Semin Respir Crit Care Med . 1998;  19 383-392
    PubMedGoogle Scholar
  • 133 Wells A U, Cullinan P, Hansell D M. Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis.  Am J Respir Crit Care Med . 1994;  149 1583-1590
    CrossrefPubMedGoogle Scholar
  • 134 Grenier P, Valeyre D, Cluzel, et al. Chronic diffuse interstitial lung disease: determination of the diagnostic value of clinical data, chest radiography, and CT and Bayesian analysis.  Radiology . 1994;  191 383-390
    CrossrefPubMedGoogle Scholar
  • 135 Colby T V, Swenson S J. Anatomic distribution and histopathologic patterns in diffuse lung disease: correlation with HRCT.  J Thorac Imaging . 1996;  11 1-26
    PubMedGoogle Scholar
  • 136 Wells A U, Rubens M B, duBois R M. Functional impairment in fibrosing alveolitis: relationship to reversible disease on thin section computed tomography.  Eur Respir J . 1997;  10 280-285
    CrossrefPubMedGoogle Scholar
  • 137 Swensen S J, Aughenbaugh G L, Myers J L. Diffuse lung disease: diagnostic accuracy of CT in patients undergoing surgical biopsy of the lung.  Radiology . 1997;  205 229-234
    CrossrefPubMedGoogle Scholar
  • 138 Wells A U, Hansell D M, Rubens M B. The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis.  Am Rev Respir Dis . 1993;  148 1076-1082
    CrossrefPubMedGoogle Scholar
  • 139 Johkoh T, Muller N L, Cartier Y. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients.  Radiology . 1999;  211 555-560
    CrossrefPubMedGoogle Scholar
  • 140 Tung K T, Wells A U, Rubens M B. Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.  Thorax . 1993;  48 334-348
    CrossrefPubMedGoogle Scholar
  • 141 Grenier P, Valeyre D, Cluzel P. Chronic diffuse interstitial lung disease: diagnostic value of chest radiography and high resolution CT.  Radiology . 1991;  179 123-132
    PubMedGoogle Scholar
  • 142 Wells A U, Hansell D M, Haslam P L. Bronchoalveolar lavage cellularity: lone cryptogenic fibrosing alveolitis compared with the fibrosing alveolitis of systemic sclerosis.  Am J Respir Crit Care Med . 1998;  157 1474-1482
    CrossrefPubMedGoogle Scholar
  • 143 Collins C D, Wells A U, Hansell D M. Observer variation in pattern type and extent of disease in fibrosing alveolitis on thin section computed tomography and chest radiography.  Clin Radiol . 1994;  49 236-240
    PubMedGoogle Scholar
  • 144 Akira M, Sakatani M, Ueda E. Idiopathic pulmonary fibrosis: progression of honeycombing at thin-section CT.  Radiology . 1993;  189 687-691
    CrossrefPubMedGoogle Scholar
  • 145 Remy-Jardin M, Giraud F, Remy J. Importance of ground glass attentuation in chronic diffuse infiltrative lung disease: pathologic CT correlation.  Radiology . 1993;  189 693-698
    CrossrefPubMedGoogle Scholar
  • 146 Muller N L, Staples C A, Miller R R. Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation.  Radiology . 1987;  165 731-734
    PubMedGoogle Scholar
  • 147 Staples C A, Muller N L, Vedal S. Usual interstitial pneumonia: correlation of CT with clinical, functional, and radiologic findings.  Radiology . 1987;  162 377-381
    PubMedGoogle Scholar
  • 148 Kazerooni E A, Martinez F J, Flint A. Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring.  AJR . 1997;  169 977-983
    CrossrefPubMedGoogle Scholar
  • 149 Muller N L, Miller R R, Webb W R. Fibrosing alveolitis: CT-pathologic correlation.  Radiology . 1986;  160 585-588
    PubMedGoogle Scholar
  • 150 Wells A, Rubens M, duBois R. Serial CT in fibrosing alveolitis: prognostic significance of the initial pattern.  AJR . 1993;  161 1159-1165
    PubMedGoogle Scholar
  • 151 Terriff B A, Kwan S Y, Chan-Yeung M M. Fibrosing alveolitis: chest radiography and CT as predictors of clinical and functional impairment at follow-up in 26 patients.  Radiology . 1992;  184 445-449
    PubMedGoogle Scholar
  • 152 Coxson H O, Hogg J C, Mayo J R. Quantification of idiopathic pulmonary fibrosis using computed tomography and histology.  Am J Respir Crit Care Med . 1997;  155 1649-1656
    PubMedGoogle Scholar
  • 153 Drent M, von Nierop M M F A, Gerritsen F A. A computer program using BALF analysis results as a diagnostic tool in interstitial lung diseases.  Am J Respir Crit Care Med . 1996;  153 736-741
    CrossrefPubMedGoogle Scholar
  • 154 Boomars K A, Wagenaar S S, Mulder P G. Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis.  Thorax . 1995;  50 1087-1092
    CrossrefPubMedGoogle Scholar
  • 155 Fireman E, Vardinon N, Burke M. Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis.  Eur Respir J . 1998;  11 706-711
    PubMedGoogle Scholar
  • 156 Ziegenhagen M W, Zabel P, Zissel G. Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity.  Am J Respir Crit Care Med . 1998;  157 762-768
    CrossrefPubMedGoogle Scholar
  • 157 Peterson M W, Monick M, Hunninghake G W. Prognostic role of eosinophils in pulmonary fibrosis.  Chest . 1987;  92 51-56
    CrossrefPubMedGoogle Scholar
  • 158 Haslam P, Turton C, Lukoszek A. Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy.  Thorax . 1980;  35 328-329
    CrossrefPubMedGoogle Scholar
  • 159 Roth C, Huchon G J, Arnoux A. Bronchoalveolar cells in advanced pulmonary sarcoidosis.  Am Rev Respir Dis . 1981;  124 9-12
    PubMedGoogle Scholar
  • 160 Gelb A F, Dreisen R B, Epstein J D. Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis: a structure-function clinical study.  Chest . 1983;  84 148-153
    PubMedGoogle Scholar
  • 161 Garcia J G, Wolven R G, Garcia P L. Assessment of interlobar variation of bronchoalveolar lavage cellular differentials in interstitial lung diseases.  Am Rev Respir Dis . 1986;  133 444-449
    PubMedGoogle Scholar
  • 162 Pantin C F, Valind S O, Sweatman M. Measures of the inflammatory response in cryptogenic fibrosing alveolitis.  Am Rev Respir Dis . 1988;  138 1234-1241
    CrossrefPubMedGoogle Scholar
  • 163 Mana J. Nuclear imaging: 67Gallium, 201thallium, 18F-labeled fluoro-2-deoxy-D- glucose positron emission tomography.  Clin Chest Med . 1997;  18 799-811
    CrossrefPubMedGoogle Scholar
  • 164 Kaplan J D, Trulock E P, Anderson D J. Pulmonary vascular permeability in interstitial lung disease: a positron emission tomographic study.  Am Rev Respir Dis . 1992;  145 1495-1498
    PubMedGoogle Scholar
  • 165 Raghu G, Chen Y Y, Rusch V. Differential proliferation of fibroblasts cultured from normal and fibrotic human lungs.  Am Rev Respir Dis . 1988;  138 703-708
    PubMedGoogle Scholar
  • 166 Raghu G, Masta S, Meyers D. Collagen synthesis by normal and fibrotic human lung fibroblasts and the effect of transforming growth factor-beta.  Am Rev Respir Dis . 1989;  140 95-100
    PubMedGoogle Scholar
  • 167 Selman M, King T E, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.  Ann Intern Med . 2001;  134 136-151
    CrossrefPubMedGoogle Scholar
  • 168 Raghu G, Striker L J, Hudson L D. Extracellular matrix in normal and fibrotic human lungs.  Am Rev Respir Dis . 1985;  131 281-289
    PubMedGoogle Scholar
  • 169 Ryu J H, Colby T V, Hartman T E. Smoking-related interstitial lung diseases: a concise review.  Eur Respir J . 2001;  17 122-132
    CrossrefPubMedGoogle Scholar
  • 170 Sato E, Koyama S, Takamizawa A. Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities.  Am J Physiol . 1999;  277 L1149-L1157
    PubMedGoogle Scholar
  • 171 MacNee W, Bridgeman M M, Marsden M. The effects of N-acetylcysteine and glutathione on smoke-induced changes in lung phagocytes and epithelial cells.  Am J Med . 1991;  91 60S-66S
    CrossrefPubMedGoogle Scholar
  • 172 Yano T, Deterding R R, Simonet W S. Keratinocyte growth factor reduces lung damage due to acid instillation in rats.  Am J Respir Cell Mol Biol . 1996;  15 433-442
    PubMedGoogle Scholar
  • 173 Popper H, Juettner F, Pinter J. The gastric juice aspiration syndrome (Mendelson syndrome): aspects of pathogenesis and treatment in the pig.  Virchows Arch A Pathol Anat Histopathol . 1986;  409 105-117
    CrossrefPubMedGoogle Scholar
  • 174 Egan J J, Woodcock A A, Stewart J P. Viruses and idiopathic pulmonary fibrosis.  Eur Respir J . 1997;  10 1433-1437
    CrossrefPubMedGoogle Scholar
  • 175 Baumgartner K B, Samet J M, Coultas D B. Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study. Collaborating Centers.  Am J Epidemiol . 2000;  152 307-315
    CrossrefPubMedGoogle Scholar
  • 176 MacNee W, Rahman I. Oxidants/antioxidants in idiopathic pulmonary fibrosis.  Thorax . 1995 (suppl 1);  50 (S53-S58)
    PubMedGoogle Scholar
  • 177 Behr J, Degenkolb B, Maier K. Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis.  Eur Respir J . 1995;  8 1286-1292
    CrossrefPubMedGoogle Scholar
  • 178 Cantin A M, Hubbard R C, Crystal R G. Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis.  Am Rev Respir Dis . 1989;  139 370-372
    CrossrefPubMedGoogle Scholar
  • 179 Behr J, Maier K, Degenkolb B. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis: adjunctive therapy to maintenance immunosuppression.  Am J Respir Crit Care Med . 1997;  156 1897-1901
    CrossrefPubMedGoogle Scholar
  • 180 Smart S J, Casale T B. Pulmonary epithelial cells facilitate TNF-alpha-induced neutrophil chemotaxis: a role for cytokine networking.  J Immunol . 1994;  152 4087-4094
    PubMedGoogle Scholar
  • 181 Parekh T, Saxena B, Reibman J. Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, TGF-beta 3) is mediated by fibronectin.  J Immunol . 1994;  152 2456-2466
    PubMedGoogle Scholar
  • 182 Hammond M E, Lapointe G R, Feucht P H. IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors.  J Immunol . 1995;  155 1428-1433
    PubMedGoogle Scholar
  • 183 Khalil N, O'Connor R N, Flanders K C. TGF-beta 1, but not TGF-beta 2 or TGF-beta 3, is differentially present in epithelial cells of advanced pulmonary fibrosis: an immunohistochemical study.  Am J Respir Cell Mol Biol . 1996;  14 131-138
    PubMedGoogle Scholar
  • 184 Southcott A M, Jones K P, Li D. Interleukin-8.  Differential expression in lone fibrosing alveolitis and systemic sclerosis. Am J Respir Crit Care Med . 1995;  151 1604-1612
    PubMedGoogle Scholar
  • 185 Piguet P F, Ribaux C, Karpuz V. Expression and localization of tumor necrosis factor-alpha and its mRNA in idiopathic pulmonary fibrosis.  Am J Pathol . 1993;  143 651-655
    PubMedGoogle Scholar
  • 186 Khalil N, O'Connor R N, Unruh H W. Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis.  Am J Respir Cell Mol Biol . 1991;  5 155-162
    PubMedGoogle Scholar
  • 187 Paakko P, Kaarteenaho-Wiik R, Pollanen R. Tenascin mRNA expression at the foci of recent injury in usual interstitial pneumonia.  Am J Respir Crit Care Med . 2000;  161 967-972
    PubMedGoogle Scholar
  • 188 Uhal B D, Joshi I, Hughes W F. Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung.  Am J Physiol . 1998;  275 L1192-L1199
    PubMedGoogle Scholar
  • 189 Ramos C, Montano M, Garcia-Alvarez J. Fibroblasts from idiopathic pulmonary fibrosis and normal lungs differ in growth rate, apoptosis, and tissue inhibitor of metalloproteinases expression.  Am J Respir Cell Mol Biol . 2001;  24 591-598
    CrossrefPubMedGoogle Scholar
  • 190 Lammi L, Ryhanen L, Lakari E. Type III and type I procollagen markers in fibrosing alveolitis.  Am J Respir Crit Care Med . 1999;  159 818-823
    PubMedGoogle Scholar
  • 191 Mattey D L, Dawes P T, Nixon N B. Transforming growth factor beta 1 and interleukin 4 induced alpha smooth muscle actin expression and myofibroblast-like differentiation in human synovial fibroblasts in vitro: modulation by basic fibroblast growth factor.  Ann Rheum Dis . 1997;  56 426-431
    PubMedGoogle Scholar
  • 192 Kuhn C, McDonald J A. The roles of the myofibroblast in idiopathic pulmonary fibrosis: ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis.  Am J Pathol . 1991;  138 1257-1265
    PubMedGoogle Scholar
  • 193 Selman M, Ruiz V, Cabrera S. TIMP-1, -2, -3, and -4 in idiopathic pulmonary fibrosis: a prevailing nondegradative lung microenvironment?.  Am J Physiol Lung Cell Mol Physiol . 2000;  279 L562-L574
    PubMedGoogle Scholar
  • 194 Clark J G, Kuhn III C. Bleomycin-induced pulmonary fibrosis in hamsters: effect of neutrophil depletion on lung collagen synthesis.  Am Rev Respir Dis . 1982;  126 737-739
    PubMedGoogle Scholar
  • 195 Thrall R S, Phan S H, McCormick J R. The development of bleomycin-induced pulmonary fibrosis in neutrophil-depleted and complement-depleted rats.  Am J Pathol . 1981;  105 76-81
    PubMedGoogle Scholar
  • 196 Helene M, Lake-Bullock V, Zhu J. T cell independence of bleomycin-induced pulmonary fibrosis.  J Leukoc Biol . 1999;  65 187-195
    PubMedGoogle Scholar
  • 197 Siminski J, Kavanagh T, Raghu G. Recombinant tumor necrosis factor is essential for pulmonary changes induced by silica in long term isolated lung cultures.  Am Rev Respir Dis . 1991;  143 A726
    PubMedGoogle Scholar
  • 198 Hunninghake G W, Kalica A R. Approaches to the treatment of pulmonary fibrosis.  Am J Respir Crit Care Med . 1995;  151 915-918
    PubMedGoogle Scholar
  • 199 Mason R J, Schwarz M I, Hunninghake G W. Pharmacological therapy for idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1999;  160 1771-1777
    PubMedGoogle Scholar
  • 200 Munger J S, Huang X, Kawakatsu H. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis.  Cell . 1999;  96 319-328
    CrossrefPubMedGoogle Scholar
  • 201 Ribeiro S M, Poczatek M, Schultz-Cherry S. The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta.  J Biol Chem . 1999;  274 13586-13593
    CrossrefPubMedGoogle Scholar
  • 202 Kelley J. Cytokines of the lung.  Am Rev Respir Dis . 1990;  141 765-788
    PubMedGoogle Scholar
  • 203 Postlethwaite A E, Keski-Oja J, Moses H L. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.  J Exp Med . 1987;  165 251-256
    CrossrefPubMedGoogle Scholar
  • 204 Khalil N, Bereznay O, Sporn M. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.  J Exp Med . 1989;  170 727-737
    CrossrefPubMedGoogle Scholar
  • 205 Giri S N, Hyde D M, Hollinger M A. Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice.  Thorax . 1993;  48 959-966
    CrossrefPubMedGoogle Scholar
  • 206 Wang Q, Wang Y, Hyde D M. Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor in hamsters.  Thorax . 1999;  54 805-812
    PubMedGoogle Scholar
  • 207 Korfhagen T R, Swantz R J, Wert S E. Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice.  J Clin Invest . 1994;  93 1691-1699
    PubMedGoogle Scholar
  • 208 Sime P J, Xing Z, Graham F L. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung.  J Clin Invest . 1997;  100 768-776
    CrossrefPubMedGoogle Scholar
  • 209 Kapanci Y, Desmouliere A, Pache J C. Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis: possible role of transforming growth factor beta and tumor necrosis factor alpha.  Am J Respir Crit Care Med . 1995;  152 2163-2169
    PubMedGoogle Scholar
  • 210 Battegay E J, Raines E W, Colbert T. TNF-alpha stimulation of fibroblast proliferation: dependence on platelet-derived growth factor (PDGF) secretion and alteration of PDGF receptor expression.  J Immunol . 1995;  154 6040-6047
    PubMedGoogle Scholar
  • 211 Postlethwaite A E, Seyer J M. Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor alpha (TNF-alpha) and a synthetic TNF-alpha 31-68 peptide.  J Exp Med . 1990;  172 1749-1756
    CrossrefPubMedGoogle Scholar
  • 212 Mauviel A, Daireaux M, Redini F. Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts.  FEBS Lett . 1988;  236 47-52
    CrossrefPubMedGoogle Scholar
  • 213 Piguet P F, Collart M A, Grau G E. Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis.  J Exp Med . 1989;  170 655-663
    CrossrefPubMedGoogle Scholar
  • 214 Ortiz L A, Lasky J, Lungarella G. Upregulation of the p75 but not the p55 TNF-alpha receptor mRNA after silica and bleomycin exposure and protection from lung injury in double receptor knockout mice.  Am J Respir Cell Mol Biol . 1999;  20 825-833
    PubMedGoogle Scholar
  • 215 Sime P J, Marr R A, Gauldie D. Transfer of tumor necrosis factor-alpha to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of transforming growth factor-beta1 and myofibroblasts.  Am J Pathol . 1998;  153 825-832
    CrossrefPubMedGoogle Scholar
  • 216 Turner-Warwick M. Precapillary systemic-pulmonary anastomoses.  Thorax . 1969;  18 225-231
    PubMedGoogle Scholar
  • 217 Peao M N, Aguas A P, de Sa M C. Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin.  Anat Rec . 1994;  238 57-67
    PubMedGoogle Scholar
  • 218 Koch A E, Polverini P J, Kunkel S L. Interleukin-8 as a macrophage-derived mediator of angiogenesis.  Science . 1992;  258 1798-1801
    PubMedGoogle Scholar
  • 219 Strieter R M, Kunkel S L, Elner V M. Interleukin-8: a corneal factor that induces neovascularization.  Am J Pathol . 1992;  141 1279-1284
    PubMedGoogle Scholar
  • 220 Strieter R M, Kunkel S L, Arenberg D A. Interferon gamma-inducible protein 10 (IP-10), a member of the C-X-C chemokine family, is an inhibitor of angiogenesis.  Biochem Biophys Res Commun . 1995;  210 51-57
    CrossrefPubMedGoogle Scholar
  • 221 Ziegenhagen M W, Schrum S, Zissel G. Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis.  J Investig Med . 1998;  46 223-231
    PubMedGoogle Scholar
  • 222 Lynch III P J, Standiford T J, Rolfe M W. Neutrophilic alveolitis in idiopathic pulmonary fibrosis: the role of interleukin-8.  Am Rev Respir Dis . 1992;  145 1433-1439
    PubMedGoogle Scholar
  • 223 Keane M P, Arenberg D A, Lynch III P J. The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis.  J Immunol . 1997;  159 1437-1443
    PubMedGoogle Scholar
  • 224 Keane M P, Belperio J A, Moore T A. Neutralization of the CXC chemokine, macrophage inflammatory protein-2, attenuates bleomycin-induced pulmonary fibrosis.  J Immunol . 1999;  162 5511-5518
    PubMedGoogle Scholar
  • 225 Keane M P, Belperio J A, Arenberg D A. IFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis.  J Immunol . 1999;  163 5686-5692
    PubMedGoogle Scholar
  • 226 Southcott A M, Hemingway I, Lorimer S. Adhesion molecule expression in the lung: a comparison between normal and diffuse interstitial lung disease.  Eur Respir J . 1998;  11 91-98
    CrossrefPubMedGoogle Scholar
  • 227 Fukuda Y, Basset F, Ferrans V J. Significance of early intra-alveolar fibrotic lesions and integrin expression in lung biopsy specimens from patients with idiopathic pulmonary fibrosis.  Hum Pathol . 1995;  26 53-61
    CrossrefPubMedGoogle Scholar
  • 228 Nakao A, Hasegawa Y, Tsuchiya Y. Expression of cell adhesion molecules in the lungs of patients with idiopathic pulmonary fibrosis.  Chest . 1995;  108 233-239
    PubMedGoogle Scholar
  • 229 van Dinther-Janssen C A, van Maarsseveen C T, Eckert H. Identical expression of ELAM-1, VCAM-1, and ICAM-1 in sarcoidosis and usual interstitial pneumonitis.  J Pathol . 1993;  170 157-164
    PubMedGoogle Scholar
  • 230 Sato N, Suzuki Y, Nishio K. Roles of ICAM-1 for abnormal leukocyte recruitment in the microcirculation of bleomycin-induced fibrotic lung injury.  Am J Respir Crit Care Med . 2000;  161 1681-1688
    PubMedGoogle Scholar
  • 231 Honda Y, Kuroki Y, Matsuura E. Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids.  Am J Respir Crit Care Med . 1995;  152 1860-1866
    CrossrefPubMedGoogle Scholar
  • 232 Honda Y, Kuroki Y, Shijubo N. Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic pulmonary fibrosis and its clinical significance.  Respiration . 1995;  62 64-69
    CrossrefPubMedGoogle Scholar
  • 233 McCormack F X, King T E, Voelker D R. Idiopathic pulmonary fibrosis: abnormalities in the bronchoalveolar lavage content of surfactant protein A.  Am Rev Respir Dis . 1991;  144 160-166
    PubMedGoogle Scholar
  • 234 Miyazaki Y, Araki K, Vesin C. Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis: a mouse model of progressive pulmonary fibrosis.  J Clin Invest . 1995;  96 250-259
    PubMedGoogle Scholar
  • 235 Hyde D M, Henderson T S, Giri S N. Effect of murine gamma interferon on the cellular responses to bleomycin in mice.  Exp Lung Res . 1988;  14 687-704
    PubMedGoogle Scholar
  • 236 Gurujeyalakshmi G, Giri S N. Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin-mouse model of lung fibrosis: downregulation of TGF-beta and procollagen I and III gene expression.  Exp Lung Res . 1995;  21 791-808
    PubMedGoogle Scholar
  • 237 Massague J. TGF-beta signal transduction.  Annu Rev Biochem . 1998;  67 753-791
    CrossrefPubMedGoogle Scholar
  • 238 Narayanan A S, Whithey J, Souza A. Effect of gamma-interferon on collagen synthesis by normal and fibrotic human lung fibroblasts.  Chest . 1992;  101 1326-1331
    PubMedGoogle Scholar
  • 239 Ihle J N. Cytokine receptor signalling.  Nature . 1995;  377 591-594
    CrossrefPubMedGoogle Scholar
  • 240 Ulloa L, Doody J, Massague J. Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway.  Nature . 1999;  397 710-713
    CrossrefPubMedGoogle Scholar
  • 241 Nakao A, Fujii M, Matsumura R. Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice.  J Clin Invest . 1999;  104 5-11
    PubMedGoogle Scholar
  • 242 Michaelson J E, Aguayo S M, Roman J. Idiopathic pulmonary fibrosis: a practical approach for diagnosis and management.  Chest . 2000;  118 788-794
    CrossrefPubMedGoogle Scholar
  • 243 Douglas W W, Ryu J H, Bjoraker J A. Colchicine versus prednisone as treatment of usual interstitial pneumonia.  Mayo Clin Proc . 1997;  72 201-209
    PubMedGoogle Scholar
  • 244 Selman M, Carrillo G, Salas J. Colchicine, D-penicillamine, and prednisone in the treatment of idiopathic pulmonary fibrosis: a controlled clinical trial.  Chest . 1998;  114 507-512
    CrossrefPubMedGoogle Scholar
  • 245 Stack B H, Choo-Kang Y F, Heard B E. The prognosis of cryptogenic fibrosing alveolitis.  Thorax . 1972;  27 535-542
    CrossrefPubMedGoogle Scholar
  • 246 Collard H R, King Jr E T. Treatment of idiopathic pulmonary fibrosis: the rise and fall of corticosteroids.  Am J Med . 2001;  110 326-328
    CrossrefPubMedGoogle Scholar
  • 247 Meier-Sydow J, Weiss S M, Buhl R. Idiopathic pulmonary fibrosis: current clinical concepts and challenges in management.  Sem Respir Crit Care Med . 1994;  15 77-96
    PubMedGoogle Scholar
  • 248 O'Donnell K, Keogh B, Cantin A. Pharmacologic suppression of the neutrophil component of the alveolitis in idiopathic pulmonary fibrosis.  Am Rev Respir Dis . 1987;  136 288-292
    PubMedGoogle Scholar
  • 249 Zisman D A, Lynch III P J, Toews G B. Cyclophosphamide in the treatment of idiopathic pulmonary fibrosis: a prospective study in patients who failed to respond to corticosteroids.  Chest . 2000;  117 1619-1626
    CrossrefPubMedGoogle Scholar
  • 250 Kolb M, Kirschner J, Riedel W. Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis.  Eur Respir J . 1998;  12 1409-1414
    CrossrefPubMedGoogle Scholar
  • 251 Baughman R, Lower E. Use of intermittent, intravenous cyclophophamide for idiopathic pulmonary fibrosis.  Chest . 1992;  102 1090-1094
    PubMedGoogle Scholar
  • 252 Dayton C S, Schwartz D A, Helmers R A. Outcome of subjects with idiopathic pulmonary fibrosis who fail corticosteroid therapy: implications for further studies.  Chest . 1993;  103 69-73
    PubMedGoogle Scholar
  • 253 Schwartz D A, vanFossen D S, Davis C S. Determinants of progression in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1994;  149 444-449
    CrossrefPubMedGoogle Scholar
  • 254 Eliasson O, Cole S, Degraff A. Adverse effects of cyclophosphamide in idiopathic pulmonary fibrosis.  Conn Med . 1985;  49 286-289
    PubMedGoogle Scholar
  • 255 van Oortegem K, Wallaert B, Marquette C H. Determinants of response to immunosuppressive therapy in idiopathic pulmonary fibrosis.  Eur Respir J . 1994;  7 1950-1957
    PubMedGoogle Scholar
  • 256 Lok S S, Smith E, Doran H M. Idiopathic pulmonary fibrosis and cyclosporine: a lesson from single-lung transplantation.  Chest . 1998;  114 1478-1481
    PubMedGoogle Scholar
  • 257 Fukazawa M, Kawano M, Hisano S. Efficacy of cyclosporin A for idiopathic pulmonary fibrosis.  Eur J Pediatr . 1990;  149 441-442
    PubMedGoogle Scholar
  • 258 Alton E W, Johnson M, Turner-Warwick M. Advanced cryptogenic fibrosing alveolitis: preliminary report on treatment with cyclosporin A.  Respir Med . 1989;  83 277-279
    CrossrefPubMedGoogle Scholar
  • 259 Moolman J A, Bardin P G, Rossouw D J. Cyclosporin as a treatment for interstitial lung disease of unknown etiology.  Thorax . 1991;  46 592-595
    CrossrefPubMedGoogle Scholar
  • 260 Venuta F, Rendina E A, Ciriaco P. Efficacy of cyclosporine to reduce steroids in patients with idiopathic pulmonary fibrosis before lung transplantation.  J Heart Lung Transplant . 1993;  12 909-914
    PubMedGoogle Scholar
  • 261 Lok S, and the Greater Manchester Lung Fibrosis Consortium. The survival of idiopathic pulmonary fibrosis patients treated with cyclosporine and cyclophosphamide.  Am J Respir Crit Care Med . 1998;  157 A278
    PubMedGoogle Scholar
  • 262 Lipsky J J. Mycophenolate mofetil.  Lancet . 1996;  348 1357-1359
    CrossrefPubMedGoogle Scholar
  • 263 Peters S G, McDougall J C, Douglas W W. Colchicine in the treatment of pulmonary fibrosis.  Chest . 1993;  103 101-104
    CrossrefPubMedGoogle Scholar
  • 264 Entzian P, Scklaak M, Seitzer U. Antiinflammatory and antifibrotic properties of colchicine: implications for idiopathic pulmonary fibrosis.  Lung . 1997;  175 41-51
    CrossrefPubMedGoogle Scholar
  • 265 Rennard S I, Bitterman P B, Ozaki T. Colchicine suppresses the release of fibroblast growth factors from alveolar macrophages in vitro: the basis of a possible therapeutic approach to the fibrotic disorders.  Am Rev Respir Dis . 1988;  137 181-185
    PubMedGoogle Scholar
  • 266 Meier-Sydow J, Rust M, Kronenberger H. Long-term follow-up of lung function parameters in patients with idiopathic pulmonary fibrosis treated with prednisone and azathioprine or D-penicillamine.  Prax Pneumol . 1979;  33 680-688
    PubMedGoogle Scholar
  • 267 Miyamoto K, Aida A, Nishimura M. Gender effect on prognosis of patients receiving long-term home oxygen therapy. The Respiratory Failure Research Group in Japan.  Am J Respir Crit Care Med . 1995;  152 972-976
    PubMedGoogle Scholar
  • 268 Strom K, Boe J. Quality assessment and predictors of survival in long-term domiciliary oxygen therapy. The Swedish Society of Chest Medicine.  Eur Respir J . 1991;  4 50-58
    PubMedGoogle Scholar
  • 269 Yoshida M, Taguchi O, Gabazza E C. The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis.  Eur Respir J . 1997;  10 2051-2054
    CrossrefPubMedGoogle Scholar
  • 270 Olschewski H, Ghofrani H A, Walmrath D. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis.  Am J Respir Crit Care Med . 1999;  160 600-607
    CrossrefPubMedGoogle Scholar
  • 271 Harris-Eze A O, Sridhar G, Clemens R E. Low-dose nebulized morphine does not improve exercise in interstitial lung disease.  Am J Respir Crit Care Med . 1995;  152 1940-1945
    PubMedGoogle Scholar
  • 272 Trulock E P. Lung transplantation.  Am J Respir Crit Care Med . 1997;  155 789-818
    CrossrefPubMedGoogle Scholar
  • 273 Arcasoy S M, Kotloff R M. Lung transplantation.  N Engl J Med . 1999;  340 1081-1091
    CrossrefPubMedGoogle Scholar
  • 274 Maurer J R, Frost A E, Estenne M. International guidelines for the selection of lung transplant candidates. The International Society for Heart and Lung Transplantation, the American Thoracic Society, the American Society of Transplant Physicians, the European Respiratory Society.  J Heart Lung Transplant . 1998;  17 703-709
    PubMedGoogle Scholar
  • 275 Hosenpud J D, Bennett L E, Keck B M. The Registry of the International Society for Heart and Lung Transplantation: seventeenth official report-2000.  J Heart Lung Transplant . 2000;  19 909-931
    CrossrefPubMedGoogle Scholar
  • 276 Iyer S N, Gurujeyalakshmi G, Giri S N. Effects of pirfenidone on transforming growth factor-b gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis.  J Pharmacol Exp Ther . 1999;  291 367-373
    PubMedGoogle Scholar
  • 277 Gurujeyalakshmi G, Hollinger M A, Giri S N. Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level.  Am J Physiol . 1999;  276 L311-L318
    PubMedGoogle Scholar
  • 278 Kaneko M, Inoue H, Nakazawa R. Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts.  Clin Exp Immunol . 1998;  113 72-76
    CrossrefPubMedGoogle Scholar
  • 279 Lee J S, Gong G, Song K S. Usual interstitial pneumonia: relationship between disease activity and the progression of honeycombing at thin-section computed tomography.  J Thorac Imaging . 1998;  13 199-203
    CrossrefPubMedGoogle Scholar
  • 280 Cain W C, Stuart R W, Lefkowitz D L. Inhibition of tumor necrosis factor and subsequent endotoxin shock by pirfenidone.  Int J Immunopharmacol . 1998;  20 685-695
    CrossrefPubMedGoogle Scholar
  • 281 Kondo H, Yonezawa Y, Ito H. Interferon-g-1, an autocrine cytokine, suppressed human fetal skin fibroblast migration into a denuded area in a cell monolayer but is not involved in the age-related decline of cell migration.  Mech Aging Dev . 1996;  87 141-153
    CrossrefPubMedGoogle Scholar
  • 282 Cornellissen A M, Von den Hoff W J, Maltha J C. Effect on interferons on proliferation and collagen synthesis of rat palatal wound fibroblasts.  Arch Oral Biol . 1999;  44 541-547
    PubMedGoogle Scholar
  • 283 Ziesche R, Hofbauer E, Wittmann K. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisone in patients with idiopathic pulmonary fibrosis.  N Engl J Med . 1999;  341 1264-1269
    CrossrefPubMedGoogle Scholar
  • 284 Majumdar S, Li D, Ansari T. Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis: a quantitative study of open lung biopsies.  Eur Respir J . 1999;  14 251-257
    PubMedGoogle Scholar
  • 285 Du Bois M R. Interferon gamma-1b for the treatment of idiopathic pulmonary fibrosis.  N Engl J Med . 1999;  341 1302-1304
    CrossrefPubMedGoogle Scholar
  • 286 Meyer K C, Raghu G. Perspectives and future advances on the diagnosis and treatment of idiopathic pulmonary fibrosis.  Lung Biol Health Dis . 1995;  80 837-874
    PubMedGoogle Scholar
  • 287 Myer A, Buhl R, Magnussen H. The effect of oral N-acetylcysteine on lung glucathione levels in idopathic pulmonary fibrosis.  Eur Respir J . 1994;  7 431-436
    CrossrefPubMedGoogle Scholar
  • 288 Demedts M, Behr J, Costabel U. IFIGENIA: an international study of N-acetylcysteine (NAC) in idiopathic pulmonary fibrosis: layout and characteristics of patients.  Am J Respir Crit Care Med . 2001;  163 A708
    PubMedGoogle Scholar
  • 289 Yano T, Deterding R R, Sinoet W S. Keratinocyte growth factor reduces lung damage due to acid instillation in rats.  Am J Respir Cell Mol Biol . 1996;  15 433-442
    PubMedGoogle Scholar
  • 290 Yi E S, Williams S T, Lee H. Keratinocyte growth factor ameliorates radiation- and bleomycin-induced lung injury and mortality.  Am J Pathol . 1996;  149 1963-1970
    PubMedGoogle Scholar
  • 291 Unemori E N, Pickford L B, Salles A L. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo.  J Clin Invest . 1996;  98 2739-2745
    PubMedGoogle Scholar
  • 292 Tan A H, Levrey C, Dahm V A. Lovastatin induces fibroblast apoptosis in vitro and in vivo: a possible therapy for fibroproliferative disorders.  Am J Respir Crit Care Med . 1999;  159 220-227
    PubMedGoogle Scholar
  • 293 Lynch III P J, McCune W J. Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.  Am J Respir Crit Care Med . 1997;  155 395-420
    PubMedGoogle Scholar