Wenjun Mao

Initial Experience of Lung Transplantation at a Single Center in China

OBJECTIVES Lung transplantation (LT) remains the only available option for patients with end-stage lung disease. Until recently, 244 lung transplantations have been performed at approximate 20 institutes in China. The aim of this article was to present the initial experience of LT at a single center in China. METHODS We performed a retrospective review of the database from The Chinese Organ Transplantation Network between January 1978 and December 2010 with detailed records available at our center. RESULTS We performed 100 of 244 lung transplantions at the Wuxi Center, The remaining procedures were performed at other institutes. The overall survival rates for these patients at 1, 2, 3, and 5 years were 73.3%, 61.6%, 53.5%, and 40.7%, respectively. The indications for lung transplantation included idiopathic pulmonary fibrosis (n = 47), chronic obstructive pulmonary disease (n = 33), silicosis (n = 5), bronchiectasis (n = 5), and Eisenmengers syndrome (n = 4). The procedure types consisted of single-lung transplantations (s; n = 72), and bilateral lung transplantations (s; n = 28). Cardiopulmonary bypass was required in 5 patients, whereas 56 required arteriovenous extracorporeal membrane oxygenation, including extended use in 3 before and 10 after LT. The main morbidities and complications after LT were sepsis (n = 11), primary graft dysfunction (PGD, n = 10), anastomotic stenosis (n = 10), acute rejection episodes (n = 25), and bronchiolitis obliterans syndrome (n = 15). In-hospital mortality was 18%, including sepsis (n = 10), PGD (n = 6), acute rejection episode (n = 1) and pulmonary infarction (n = 1). The mean survival time was 3.4 years. CONCLUSIONS In China, lung transplantation may offer a viable therapy for patients with various end-stage pulmonary conditions. The initiation of LT should focus on improving the survival rate by increased clinical practice.

Distinct Phenotypes of Primary Graft Dysfunction After Lung Transplantation

Affi liations: From the Department of Clinical Epidemiology (Drs Søgaard, Nørgaard, and Thomsen and Ms Nielsen), Institute of Clinical Medicine, Aarhus University Hospital; and Department of Clinical Microbiology (Drs Kornum and Schønheyder), Aalborg Hospital, Aarhus University Hospital. Funding/Support: This study was supported by the Klinisk Epidemiologisk Forskningsfond at Aarhus University. Financial/nonfi nancial disclosures: The authors have reported to CHEST the following confl icts of interest: Dr Schønheyder is coinventor of a patent for an adjuvant of conjugated pneumococcal vaccine. Drs Søgaard, Nørgaard, Kornum, and Thomsen and Ms Nielsen have reported that no potential confl icts of interest exist with any companies/organizations whose products or services may be discussed in this article . Correspondence to: Mette Søgaard, DVM, PhD, Department of Clinical Epidemiology, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark; e-mail: mette.soegaard@ki.au.dk

Regulation of lung transplantation in China

To the Editor: We read with great interest the article by Lavee and colleagues, who presented and reviewed the current status of heart and lung transplantation in China. The authors provided insights into the controversial issues of transplant programs that have existed for a long time. Although acute criticisms of organ donation were conducted by professional societies and other organizations, some advances have been recently achieved. As we represent the Chinese management unit for the lung transplant registry, we highlight some positive developments with regard to the transplant profession and present some guidelines for addressing the future growth of lung transplant programs in China. It is well known that there is a lack of wide acceptance of the concept of brain death in China, because, in traditional Chinese culture, death only occurs after cardiac death with cessation of respiration. Second, legislation regarding brain death has not yet fully come into effect. With organ donation after brain death (DBD) considered unacceptable by most citizens, there was an increase in under-regulated transplant practices, given that, in a country of 1.3 billion people, there is a large population of patients requiring organ transplantation to extend life expectancy. Despite that unfortunate development, much success has also been achieved. In 2003, the Chinese Ministry of Health (CMH) published official criteria for brain death, which indirectly promoted transplantation from brain-dead donors. Then, the CMH established a government policy in 2007 to oversee organ transplantation so as to limit the growth of inadequately regulated transplantation. A total of 282 organs from 63 brain-dead donors had been utilized for transplantation until 2007, and the number of qualifying hospitals had largely decreased. In April 2008, however, the CMH organized a symposium to discuss the effect of brain death criteria in China. The CMH has since aimed to widely promote the brain death criterion and enact legislation for brain death when the concept finally becomes widely accepted. Lavee et al commented on those “whose consent is either non-existent or ethically invalid, and whose demise may be timed for the convenience of the waiting recipient—that is,

Lung transplantation for lung cancer.

We read with interest the article by Ahmad and associates [1] regarding the utility of lung transplantation for lung cancer, which concluded that lung transplantation was a reasonable option for patients who did not benefit from medical or surgical therapies to control their cancers. However, we would like to raise some questions that require further clarifications. Lung cancer was earlier considered an absolute contraindication for lung transplantation, but study has begun to focus on the benefits for long-term survival after lung transplantation for bronchoalveolar carcinoma (BAC) [2, 3]. However, lung transplantation is not supported for patients with other types of bronchogenic carcinoma owing to high risk of cancer recurrence [2]. Ahmad and colleagues [1] comment that “lymph node metastases did not preclude survival.” Despite this, does N1 or N2 disease as a marker of tumor metastasis actually not predict the outcome of transplanted patients? Perrot and coworkers [3] have demonstrated that patients with stage II or III bronchogenic carcinoma had worse prognosis than patients with stage I, and usually succumb to cancers due to extensive tumor recurrence. Thus, lymph node invasion in these patients causes a clinical dilemma of recipient selection and greatly affects actual survival. Patients with suspicious N2 nodes should be investigated by mediastinoscopy as discussed by Ahmad and colleagues [1]; N2positive lung cancer is generally considered a contraindication to surgical therapy, even though surprisingly reasonable survival was achieved in this study. Endobronchial ultrasound–fine-needle aspiration in addition tomediastinoscopycan facilitate thedetection of N1 disease; N1 disease rather than N2 disease as the cutoff for exclusion of lung transplantation may turn to optimal selection of patients. Thus, N2 disease as the cutoff is not convincing. Whether patients with bronchogenic carcinoma benefit from lung transplant should be confirmed by a large prospective trial. However, several ethical issues related to lung transplant should be resolved. Patients with bronchogenic carcinoma receiving lung transplants only accounted for 0.1% of the total number, and waiting-list mortality is commonly ascribed to donor scarcity; therefore, how to allocate the limited donors will be discussed before the trial is launched. Should patients not amenable to surgical resection (no N2 disease) receive lung transplant or chemotherapy-based treatment? Transplant is inadequate for some patients who can benefit largely from chemotherapy. Furthermore, whether chemotherapy should be performed after lung transplant remains undecided. In addition, it is still unknown whether postoperative immunosuppressive regimens can increase the risk of cancer relapse, and that requires the proof of further research.

Role of extracorporeal life support in bridging patients to pulmonary transplantation.

Pulmonary Transplantation We read with great interest the recently published article in Transplantation by Lang et al. (1) regarding the utility of extracorporeal membrane oxygenation (ECMO) as a bridging strategy to primary pulmonary transplantation. They studied 38 patients undergoing ECMO as a bridge to transplantation with 26 of the 34 transplant patients discharged from the hospital and concluded that transplantation of patients after bridging with ECMO is reliable with acceptable outcome. Bridging patients with ECMO represents optimal therapy for circulatory and respiratory support when traditional therapy failed. The authors should be congratulated for their great effort. However, we would like to raise some questions that need clarifications. A total of 102 postoperative complications were reported in 88 patients bridged with extracorporeal life support (ECLS) in the article’s Table 4, wherein 13 were neurologic complications, which is quite different from that reported by Lang et al. (1) (13/102 vs. 17/44, twosided W test, PG0.01). It is intriguing that why profuse complications associated with neurology developed in 34 patients. The most frequent complications encountered during ECLS were hemorrhage, cannulation site complications, renal failure, sepsis, and neurologic complications (2, 3). After some thorough review, it is difficult to precisely explain the difference of complications between the anterior published articles and that of Lang et al. (1) indeed, although some potential risk factors may contribute to the disparity. Hartwig et al. (4) reported that patients on arteriovenous (V-A) ECLS showed significantly higher rates of neurologic complications when compared with venovenous ECLS; never theless, there are 12 (n=34, 35.3%) patients receiving V-A ECMO support to lung transplantation (1), whereas 35 (n=88, 39.8%) patients reported in Table 4 underwent transplantation after V-A ECMO bridge (two-sided W test, P90.05). As a consequence, modality is inadequate to determine the development of neurologic complications while on ECMO bridge, which may be largely ascribed to some confounding factors including patient management and selection, more critical illness, patient’s unwillingness to accept the invasive intervention, and lung transplantation per se. Moreover, preoperative ECMO had been proven to be a strong risk factor for mortality after transplantation in multivariable analysis (5). Thus, highly selected patients considered under ECLS bridge were likely to benefit from optimal support device when its support efficacy and adverse effects were taken into account. Twenty-six complications were found before donor lungs became available when patients in Table 4 were bridged with ECLS, which may have an adverse effect on outcome. However, no description was provided by Lang et al. (1) to clarify the adverse effects of patients who underwent transplantation while awaiting on the support device. In addition, the authors omitted the morbidity during the long-term follow-up period, which represented the quality of life in these recipients discharged from the hospital. The authors only mentioned causes of death of these patients, whereas the adverse effects are particularly helpful for the readers to judge ECLS under current medical circumstances and draw some conclusions. Bridging device mode and configuration should be individualized according to different clinical situations as reported by the authors (1). V-A ECMO is recommended when patients complicated with hypoxemic respiratory failure and hemodynamic compromise; venovenous ECMO is preferred while hypoxemia with PCO2 elevation occurs but with stable hemodynamics; and pumpless lung assist device Novalung becomes an useful strategy for isolated hypercapnemia, resulting in sufficient carbon dioxide removal (6). All the three modalities reflect invasive interventions that introduce different risks of complications to patients at disparate situations. The authors included in the retrospective study patients undergoing different bridging modalities to arrive at combined results, by which significant bias may be produced by confounding factors not accounted for. Namely, the combined analysis only represents the global results instead of separate result for each modality, respectively; therefore, the comparison by different modalities is essential to clarify the bridging efficacy objectively. In the statistical analysis, the authors used the two-sided chi-square test for the association of the clinical characteristics among three different groups (gender, diagnosis, and bridge type); however, the questions were raised because the choice of statistical method for categorical characteristics in Table 1 was confusing. From our perspective, Fisher exact test for the comparison of gender (fourfold table) is more suitable than two-sided chi-square test because the total frequency is less than 40 by calculation; moreover, the comparison of diagnosis and bridge type (2 4 table) should also be conducted with Fisher exact test, given the reason that some theoretical frequency was less than 1. These data analyzed by different statistical methods may turn to disparate results.

Concerns Raised by Lung Size-Mismatched Transplantation

Correspondence 4 . Villiot-Danger JC , Villiot-Danger E , Borel JC , Pépin JL , Wuyam B , Vergès JS . Respiratory muscle endurance training in obese patients . Int J Obes (Lond) . 2011 ; 35 ( 5 ): 692 699 . 5 . National Institutes of Health Clinical Center . Obese patients with obstructive sleep apnea syndrome (OSAS) and exercise training (OBEX1). NCT01155271. ClinicalTrials.gov . Bethesda, MD: National Institutes of Health; 2010. http:// clinicaltrials.gov/ct2/show/NCT01155271. Updated March 13, 2012. 6 . Jordan KE , Ali M , Shneerson JM . Attitudes of patients towards a hospital-based rehabilitation service for obesity hypoventilation syndrome . Thorax . 2009 ; 64 ( 11 ): 1007 .