Inhaled Cyclosporine in Lung Transplantation
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《新英格兰医药杂志》
To the Editor: The report by Iacono and colleagues (Jan. 12 issue)1 on the effect of inhaled cyclosporine in lung-transplant recipients raises important questions that need further clarification. Although the authors found that inhaled cyclosporine reduced the two- and three-year prevalence of the bronchiolitis obliterans syndrome, as compared with placebo, it is very surprising in the modern era of lung transplantation to find such a high prevalence of this syndrome: about 70 and 65 percent after two and three years, respectively, in the treated group, on the basis of spirometry, as compared with 50 and 30 percent, respectively, in the placebo group.1 In the recent registry report of the International Society for Heart and Lung Transplantation (ISHLT),2 the mean two- and three-year survival free of bronchiolitis obliterans was 80 and 71 percent, respectively, which is similar to our own experience.3 This very high prevalence (especially in the placebo group) may be one of the possible explanations for the beneficial effect of inhaled cyclosporine in the study by Iacono et al., and therefore this study certainly needs verification in patients with a "normal" prevalence of this syndrome.
Geert M. Verleden, Ph.D.
Lieven J. Dupont, Ph.D.
University Hospital Gasthuisberg
3120 Leuven, Belgium
geert.verleden@uz.kuleuven.ac.be
References
Iacono AT, Johson BA, Grgurich WF, et al. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med 2006;354:141-150.
Trulock EP, Edwards LB, Taylor DO, Boucek MM, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult lung and heart-lung transplant report -- 2005. J Heart Lung Transplant 2005;24:956-967.
Verleden GM, Egan J, Israel-Biet D, et al. Chronic lung allograft rejection: prevalence, pathology, risk factors and pathophysiology. Eur Respir Monogr 2004;29:1-16.
The authors reply: Poor survival in lung transplantation results from a relatively unvarying frequency of bronchiolitis obliterans.1,2 Methodologic differences between our study and the ISHLT registry may account for discrepancies in the incidence of bronchiolitis obliterans. We report survival free of bronchiolitis obliterans (with bronchiolitis obliterans and death as the end points), whereas freedom from bronchiolitis obliterans (with death censored) was reported by the ISHLT, resulting in a higher incidence of the bronchiolitis obliterans syndrome in our population. In our study, the rate of freedom from bronchiolitis obliterans (with death censored) at three years after lung transplantation was 71 percent in the cyclosporine group and 46 percent in the placebo group. This rate of bronchiolitis obliterans in the placebo group is similar to that reported by Verleden et al., as well as that reported by major transplantation centers in the United States.3,4 Furthermore, the status of patients with respect to bronchiolitis obliterans at one year was known for 6407 of the more than 13,007 patients who were included in the ISHLT study, whereas in our study there was 100 percent follow-up. Since a substantial proportion of those in the ISHLT registry for whom data on follow-up were unavailable could have had bronchiolitis obliterans, this possibility could account for a spurious reduction in the rate of bronchiolitis obliterans.
Aldo T. Iacono, M.D.
University of Maryland School of Medicine
Baltimore, MD 21201-1192
aiacono@medicine.umaryland.edu
Bruce A. Johnson, M.D.
Timothy E. Corcoran, Ph.D.
University of Pittsburgh Medical Center
Pittsburgh, PA 15213-2582
References
Trulock EP, Edwards LB, Taylor DO, et al. The Registry of the International Society for Heart and Lung Transplantation: twentieth official adult lung and heart-lung transplant report -- 2003. J Heart Lung Transplant 2003;22:625-635.
DeCamp MM Jr. Inhaled cyclosporine -- a breath of fresh air? N Engl J Med 2006;354:191-193.
Reichenspurner H, Girgis RE, Robbins RC, et al. Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation. Ann Thorac Surg 1996;62:1467-1473.
Meyers BF, Lynch J, Trulock EP, Guthrie TJ, Cooper JD, Patterson GA. Lung transplantation: a decade of experience. Ann Surg 1999;230:362-371.
Geert M. Verleden, Ph.D.
Lieven J. Dupont, Ph.D.
University Hospital Gasthuisberg
3120 Leuven, Belgium
geert.verleden@uz.kuleuven.ac.be
References
Iacono AT, Johson BA, Grgurich WF, et al. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med 2006;354:141-150.
Trulock EP, Edwards LB, Taylor DO, Boucek MM, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult lung and heart-lung transplant report -- 2005. J Heart Lung Transplant 2005;24:956-967.
Verleden GM, Egan J, Israel-Biet D, et al. Chronic lung allograft rejection: prevalence, pathology, risk factors and pathophysiology. Eur Respir Monogr 2004;29:1-16.
The authors reply: Poor survival in lung transplantation results from a relatively unvarying frequency of bronchiolitis obliterans.1,2 Methodologic differences between our study and the ISHLT registry may account for discrepancies in the incidence of bronchiolitis obliterans. We report survival free of bronchiolitis obliterans (with bronchiolitis obliterans and death as the end points), whereas freedom from bronchiolitis obliterans (with death censored) was reported by the ISHLT, resulting in a higher incidence of the bronchiolitis obliterans syndrome in our population. In our study, the rate of freedom from bronchiolitis obliterans (with death censored) at three years after lung transplantation was 71 percent in the cyclosporine group and 46 percent in the placebo group. This rate of bronchiolitis obliterans in the placebo group is similar to that reported by Verleden et al., as well as that reported by major transplantation centers in the United States.3,4 Furthermore, the status of patients with respect to bronchiolitis obliterans at one year was known for 6407 of the more than 13,007 patients who were included in the ISHLT study, whereas in our study there was 100 percent follow-up. Since a substantial proportion of those in the ISHLT registry for whom data on follow-up were unavailable could have had bronchiolitis obliterans, this possibility could account for a spurious reduction in the rate of bronchiolitis obliterans.
Aldo T. Iacono, M.D.
University of Maryland School of Medicine
Baltimore, MD 21201-1192
aiacono@medicine.umaryland.edu
Bruce A. Johnson, M.D.
Timothy E. Corcoran, Ph.D.
University of Pittsburgh Medical Center
Pittsburgh, PA 15213-2582
References
Trulock EP, Edwards LB, Taylor DO, et al. The Registry of the International Society for Heart and Lung Transplantation: twentieth official adult lung and heart-lung transplant report -- 2003. J Heart Lung Transplant 2003;22:625-635.
DeCamp MM Jr. Inhaled cyclosporine -- a breath of fresh air? N Engl J Med 2006;354:191-193.
Reichenspurner H, Girgis RE, Robbins RC, et al. Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation. Ann Thorac Surg 1996;62:1467-1473.
Meyers BF, Lynch J, Trulock EP, Guthrie TJ, Cooper JD, Patterson GA. Lung transplantation: a decade of experience. Ann Surg 1999;230:362-371.