Background: The existence of antineutrophil cytoplasmic antibody (ANCA)-positive pulmonary fibrosis (PF) has recently been recognized. Objectives: The aim of this study was to clarify whether there is any difference in the clinical features between ANCA-positive PF and ANCA-negative PF. Methods: A retrospective study was carried out on 53 patients with idiopathic PF whose myeloperoxidase (MPO)- and proteinase 3 (PR3)-ANCA levels were measured. After dividing the patients into ANCA-positive and ANCA-negative PF, we compared their symptoms, pulmonary function tests, chest CT findings, bronchoalveolar lavage findings, the effects of therapy and survival rates. Results: 17 of the 53 patients with idiopathic PF were MPO-ANCA-positive, 2 were PR3-ANCA-positive and 34 were negative for both ANCA types. Lactate dehydrogenase was lower in ANCA-positive PF than in ANCA-negative PF. However, there was no significant difference in the symptoms, lung function tests, CT findings and bronchoalveolar lavage findings. Corticosteroid therapy tended to be more effective in ANCA-positive PF, but the overall survival rate in ANCA-positive PF was not different from that in ANCA-negative PF. However, the low-titer (<50 EU) group showed better survival than the high-titer (≥50 EU) group in ANCA-positive PF. ANCA titers of the patients who developed microscopic polyangiitis were higher than of those who did not develop it in ANCA-positive PF. Conclusions: Our studies showed little difference in the clinical features between ANCA-positive and ANCA-negative PF. However, it may be important to measure ANCA when idiopathic PF is diagnosed, because a high titer of ANCA suggests a poor prognosis and the association with microscopic polyangiitis.

American Thoracic Society/European Respiratory Society: International multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277–304.
Nada AK, Torres VE, Ryu JH, Lie JT, Holley KE: Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients. Mayo Clin Proc 1990;65:847–856.
Davies DJ, Moran JE, Niall JF, Ryan GB: Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed) 1982;285:606.
Lüdemann J, Utecht B, Gross WL: Anti-neutrophil cytoplasm antibodies in Wegener’s granulomatosis recognize an elastinolytic enzyme. J Exp Med 1990;171:357–362.
Falk RJ, Jennette JC: Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med 1988;318:1651–1657.
van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA, van der Giessen M, van der Hem GK, The TH: Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. Lancet 1985;1:425–429.
Tervaert JW, van der Woude FJ, Fauci AS, et al: Association between active Wegener’s granulomatosis and anticytoplasmic antibodies. Arch Intern Med 1989;149:2461–2465.
Tervaert JW, Goldschmeding R, Elema JD, Limburg PC, van der Giessen M, Huitema MG, Koolen MI, Hené RJ, The TH, van der Hem GK, van der Borne AE, Kallenberg CGM: Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum 1990;33:1264–1272.
Velosa JA, Homburger HA, Holley KE: Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis. Mayo Clin Proc 1993;68:561–565.
Bosch X, Guilabert A, Font J: Antineutrophil cytoplasmic antibodies. Lancet 2006;368:404–418.
Nölle B, Specks U, Lüdemann J, Rohrbach MS, DeRemee RA, Gross WL: Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener glanulomatosis. Ann Intern Med 1989;111:28–40.
ter Maaten JC, Franssen CF, Gans RO, van Schijndal RJ, Hoorntje SJ: Respiratory failure in ANCA-associated vasculitis. Chest 1996;110:357–362.
Savige J, Gills D, Benson E, Davies D, Esnault V, Falk RJ, Hagen EC, Jayne D, Jennette JC, Paspaliaris B, Pollock W, Pusey C, Savage CO, Silvestrini R, van der Woude F, Wieslander J, Wiik A: International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 1999;111:507–513.
Mura M, Ferretti A, Ferro O, Zompatori M, Cavalli A, Schiavina M, Fabbri M: Functional predictors of exertional dyspnea, 6-min walking distance and HRCT fibrosis score in idiopathic pulmonary fibrosis. Respiration 2006;73:495–502.
Ryu YJ, Chung MP, Han J, Kim TS, Lee KS, Chun EM, Kyung SY, Jeong SH, Colby TV, Kim H, Kwon OJ: Bronchoalveolar lavage in fibrotic idiopathic interstitial pneumonias. Respir Med 2007;101:655–660.
Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K: KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis 1993;148:637–642.
Kuroki Y, Fukada Y, Takahashi H, Akino T: Monoclonal antibodies against human pulmonary surfactant apoproteins: specificity and application in immunoassay. Biochim Biophys Acta 1985;836:201–209.
Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP: Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199–203.
Noël LH, Geffriaud C, Chauveau D, Houhou S, Landais P, Kirhaoui F, Nusbaum P, Gouarin C, O’Donoghue D, Halbwachs-Mecarelli L, Grünfeld JP: Antineutrophil cytoplasm antibodies: diversity and clinical application. Adv Nephrol Necker Hosp 1993;22:237–267.
DeRemee RA, Homburger HA, Specks U: Lesions of the respiratory tract associated with findings of anti-neutrophil cytoplasmic autoantibodies with a perinuclear staining pattern. Mayo Clin Proc 1994;69:819–824.
Arimura Y, Minoshima S, Tanaka U, Fujii A, Kobayashi M, Nakabayashi K, Kitamoto K, Nagasawa T: Pulmonary involvement in patients with myeloperoxidase specific antineutrophil cytoplasmic antibody (in Japanese). Ryumachi 1995;35:46–58.
Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, Bando M, Sugiyama Y, Totani Y, Ishizaki T, Ichiyasu H, Suga M, Hamada H, Kohno N: Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 2006;11:164–168.
Homma S, Matsushita H, Nakata K: Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitides. Respirology 2004;9:190–196.
Ando Y, Okada F, Matsumoto S, Mori H: Thoracic manifestation of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related disease: CT findings in 51 patients. J Comput Assist Tomogr 2004;28:710–716.
Nagai S, Kitaichi M, Itoh H, Nishimura K, Izumi T, Colby TV: Idiopathic nonspecific interstitial pneumonia/fibrosis: Comparison with idiopathic pulmonary fibrosis and BOOP. Eur Respir J 1998;12:1010–1019.
ter Maaten JC, Franssen CF, Gans RO, van Schijndel RJ, Hoorntje SJ: Respiratory failure in ANCA-associated vasculitis. Chest 1996;110:357–362.
Haworth SJ, Savage COS, Carr D, Hughes JMB, Rees AJ: Pulmonary haemorrhage complicating Wegener’s granulomatosis and microscopic polyarteritis. Br Med J 1985;290:1775–1778.
Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ: Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996;7:23–32.
Eschun GM, Mink SN, Sharma S: Pulmonary interstitial fibrosis as a presenting manifestation in perinuclear antineutrophilic cytoplasmic antibody microscopic polyangiitis. Chest 2003;123:297–301.
Yumura W, Itabashi M, Ishida-Okawara A, Tomizawa K, Yamashita J, Kaneshiro Y, Nihei Y, Suzuki K: A novel mouse model for MPO-ANCA-associated glomerulonephritis. Microbiol Immunol 2006;50:149–157.
Brown KK: Pulmonary vasculitis. Proc Am Thorac Soc 2006;3:48–57.
Frankel SK, Cosgrove GP, Fischer A, Meehan RT, Brown KK: Update in the diagnosis and management of pulmonary vasculitis. Chest 2006;129:452–465.
Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniené J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group: A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349:36–44.
Japanese Respiratory Society: Idiopathic Interstitial Pneumonias: Diagnosis and Treatment. Nankodo, Tokyo, 2004.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.