Progression of Fibrosis in Usual Interstitial Pneumonia: Serial Evaluation of the Native Lung after Single Lung Transplantation

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Usual interstitial pneumonia (UIP) is the histopathological pattern identifying patients with the clinical entity of IPF. Despite aggressive immunosuppressive therapy the clinical course is usually dismal. For selected patients only lung transplantation improves prognosis and quality of life. After lung transplantation patients often receive a potent cyclosporine-based immunosuppressive therapy. Some reports suggest that cyclosporine has the potential to prevent progression of fibrosis. Objective: In patients with single lung transplantation (sLTx) for UIP we evaluated the effect of cyclosporine-based immunosuppressive therapy on progression of fibrosis using a high-resolution computed tomography (HRCT) scoring system. Methods: This retrospective observational study included 13 patients (24–64 years old) with histologically confirmed UIP who had HRCT scans preceding and following sLTx and who survived at least 6 months after sLTx. All patients were initially treated with cyclosporin A, prednisone and azathioprine. Three radiologists analyzed HRCT scans by setting a score regarding fibrosis [fibrosis score (FS); range 0–5 for each lobe] and ground-glass opacity [ground-glass score (GGS); range 0–5 for each lobe]. A comparison of serial changes (interval: 12–96 months posttransplant, 2–4 HRCT examinations/patient) was performed with the sign test. Results: Mean pretransplant FS and GGS of the nontransplanted lung were 1.80 and 1.61, respectively. Comparing pre- and posttransplant HRCT scans, mean lung FS significantly increased (0.35 ± 0.15/year; p = 0.00024), while GGS tended to decrease (0.06 ± 0.26/year; p = 0.5). Conclusion: A cyclosporin A based triple immunosuppressive regimen following sLTx does not seem to prevent progression of the fibrotic changes of the native lung in patients with IPF.

[1]  H. Collard,et al.  Current perspectives on the treatment of idiopathic pulmonary fibrosis. , 2006, Proceedings of the American Thoracic Society.

[2]  Johny Verschakelen,et al.  High-dose acetylcysteine in idiopathic pulmonary fibrosis. , 2005, The New England journal of medicine.

[3]  S. Kudoh,et al.  Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. , 2005, American journal of respiratory and critical care medicine.

[4]  Nicola Sverzellati,et al.  Diagnostic Imaging of Diffuse Infiltrative Disease of the Lung , 2004, Respiration.

[5]  G. Raghu,et al.  A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. , 2004, The New England journal of medicine.

[6]  E. White,et al.  Pathogenetic mechanisms in usual interstitial pneumonia/idiopathic pulmonary fibrosis , 2003, The Journal of pathology.

[7]  A. Kurosaki,et al.  [Cyclosporin A treatment of interstitial pneumonia]. , 2003, Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society.

[8]  Y. Ohtani,et al.  Cyclosporin A followed by the treatment of acute exacerbation of idiopathic pulmonary fibrosis with corticosteroid. , 2003, Internal medicine.

[9]  Marshall I Hertz,et al.  The registry of the International Society for Heart and Lung Transplantation: twentieth official adult heart transplant report--2003. , 2003, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[10]  E. Trulock,et al.  The Registry of the International Society for Heart and Lung Transplantation: Twentieth Official adult lung and heart-lung transplant report--2003. , 2003, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[11]  M. Mishima,et al.  Serial Evaluation of High-Resolution Computed Tomography Findings in Patients with Idiopathic Pulmonary Fibrosis in Usual Interstitial Pneumonia , 2002, Respiration.

[12]  D. A. Schwartz,et al.  Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working group. , 2002, American journal of respiratory and critical care medicine.

[13]  M. Wahidi,et al.  Progression of idiopathic pulmonary fibrosis in native lungs after single lung transplantation. , 2002, Chest.

[14]  Paul J. Friedman,et al.  American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors , 2002, American journal of respiratory and critical care medicine.

[15]  M. Kitaichi,et al.  Usual Interstitial Pneumonia: Idiopathic Pulmonary Fibrosis versus Collagen Vascular Diseases , 2001, Respiration.

[16]  D. Schroeder,et al.  Idiopathic pulmonary fibrosis: Impact of oxygen and colchicine, prednisone, or no therapy on survival. , 2000, American journal of respiratory and critical care medicine.

[17]  Arnold Simanowitz,et al.  international consensus statement , 2000 .

[18]  American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). , 2000, American journal of respiratory and critical care medicine.

[19]  David A. Lynch,et al.  Idiopathic pulmonary fibrosis: Diagnosis and treatment: International Consensus Statement , 2000 .

[20]  M. Kitaichi,et al.  Hospital-based historical cohort study of 234 histologically proven Japanese patients with IPF. , 1999, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[21]  J. Egan,et al.  Idiopathic pulmonary fibrosis and cyclosporine: a lesson from single-lung transplantation. , 1998, Chest.

[22]  M A Schork,et al.  Idiopathic pulmonary fibrosis: predicting response to therapy and survival. , 1998, American journal of respiratory and critical care medicine.

[23]  R. Hubbard,et al.  Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. , 1998, Chest.

[24]  K P Offord,et al.  Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. , 1998, American journal of respiratory and critical care medicine.

[25]  I. D. Johnston,et al.  British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society. , 1997, Thorax.

[26]  I. D. Johnston,et al.  Mortality rates from cryptogenic fibrosing alveolitis in seven countries. , 1996, Thorax.

[27]  W. Black,et al.  The epidemiology of interstitial lung diseases. , 1994, American journal of respiratory and critical care medicine.

[28]  M. Akira,et al.  Idiopathic pulmonary fibrosis: progression of honeycombing at thin-section CT. , 1993, Radiology.

[29]  D. Hansell,et al.  The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis. , 1993, The American review of respiratory disease.

[30]  N L Müller,et al.  Fibrosing alveolitis: chest radiography and CT as predictors of clinical and functional impairment at follow-up in 26 patients. , 1992, Radiology.

[31]  G. Raghu,et al.  Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. , 1991, The American review of respiratory disease.

[32]  E. Alton,et al.  Advanced cryptogenic fibrosing alveolitis: preliminary report on treatment with cyclosporin A. , 1989, Respiratory medicine.

[33]  R. Rudd,et al.  Cryptogenic fibrosing alveolitis. Relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis. , 1981, The American review of respiratory disease.