Text B Lung Transplantation

Lung transplantation is a therapeutic consideration for patients with most nonmalignant end－stage lung diseases．After an initial period of rapid growth from1990 through 1995，activity has increased slowly to 1，700 transplants per year worldwide．The demand for transplantation exceeds the supply of donor organs，and the waiting time is often lengthy．Recognizing the window of opportunity for transplantation in the clinical course of various lung diseases is crucial because deaths while awaiting transplantation are not unusual．However，in appropriately selected recipients，transplantation prolongs survival and improves quality of life，but it is also associated with significant morbidity and mortality．

Indications

The indications for lung transplantation span the gamut of lung diseases． The distribution reflects the prevalence and natural history of the diseases，and the most common indications are chronic obstructive pulmonary disease（COPD）， idiopathic pulmonary fibrosis（IPF），cystic fibrosis（CF），α1－antitrypsin deficiency emphysema，and primary pulmonary hypertension（PPH）．Others comprise many less prevalent lung diseases，i．e．sarcoidosis，bronchiectasis， Eisenmenger syndrome etc．

Recipient Selection

Transplantation should be considered when other therapeutic options have been exhausted and when the patient's prognosis will be improved by the procedure．Survival rates after transplantation can be compared with predictive indices for the underlying disease，but each patient's clinical course must be integrated into the assessment，too．In any case，projected survival after transplantation should exceed life expectancy without the procedure．Candidates for lung transplantation are thoroughly screened for any comorbidity that might adversely affect the outcome．Suitable candidates should have clinically and physiologically severe lung disease，but otherwise they must be in reasonably good health．The upper age limit is 65 years at most centers．

Typical exclusions include HIV infection，chronic hepatitis B antigenemia or chronic active hepatitis C infection，uncured malignancy，active cigarette smoking，drug or alcohol dependency or abuse，uncontrolled or untreatable pulmonary or extrapulmonary infection，irreversible physical deconditioning， chronic noncompliance with medical care，and significant disease of any vital organ other than the lungs．Other problems that might increase the risk of complications or might be aggravated by the posttransplantation medical regimen constitute relative contraindications．1 Some typical issues are ventilator－dependent respiratory failure，previous thoracic surgical procedures， osteoporosis，systemic hypertension，diabetes mellitus，obesity or cachexia， and psychosocial problems．The potential impact of these and many other factors has to be judged in clinical context to determine an individual candidate's suitability for transplantation．

Waiting List and Organ Allocation

Organ allocation policies are influenced by ethical，medical，geographical， and political factors，and systems vary from country to country．Regardless of the system，potential recipients are placed on a waiting list and must be matched for blood group compatibility and，with some latitude，for lung size with an acceptable donor．In the United States a priority algorithm for allocating donor lungs was implemented in May 2005．Priority is determined by a lung allocation score that weighs both the patient's risk of death on the waiting list and the likelihood of survival after transplantation．Both the type and the severity of lung disease affect the allocation score；relevant parameters must be updated periodically but can be submitted whenever the patient's condition changes．However，this priority system does not diminish the importance of timely referral．Under the previous seniority system，the median time to transplantation was 1，104 days for patients who initially registered on the national waiting list in 1998．Approximately 10％of the patients on the waiting list died before transplantation，but the death rate while waiting was much higher for patients with IPF，PPH，or CF than for those with COPD or α1－antitrypsin deficiency emphysema．

Transplant Procedure

Bilateral transplantation is mandatory for bronchiectasis because the risk of spillover infection from a remaining native lung precludes single lung transplantation．Heart－lung transplantation is obligatory for Eisenmenger syndrome with complex anomalies that cannot be readily repaired in conjunction with lung transplantation and for concomitant end－stage lung and heart disease．2 However，cardiac replacement is not necessary for cor pulmonale because right ventricular function will recover when pulmonary vascular afterload is normalized by lung transplantation．

Either bilateral or single lung transplantation is an acceptable alternative for other diseases unless there is a special consideration．Bilateral transplantation provides more reserve lung function as a buffer against complications，and it has been increasingly utilized for many indications．In recipients with COPD andα1－antitrypsin deficiency emphysema，survival has been significantly better after bilateral transplantation，but there has not been a significant difference in survival between the two procedures for other diseases．3

Living donor lobar transplantation has a limited role in adult lung transplantation．It has been performed predominantly in teenagers or young adults with CF．A right lower lobe is obtained from one living donor and a left lower lobe from another，and these lobes are implanted to replace the right and left lungs，respectively，in the recipient．Since a lobe must replace a whole lung，donor－recipient size considerations are crucial．The results have been comparable to those with transplantation from cadaveric donors．The usual morbidities associated with a lobectomy have been encountered in the donors， but no death has yet been reported．Because of ethical concerns，this approach is usually restricted to patients who are unlikely to survive the wait for a cadaveric donor．

Posttransplantation Management

Induction therapy with an antilymphocyte globulin or an interleukin 2 receptor antagonist is utilized by some centers，and a three－drug maintenance immunosuppressive regimen that includes a calcineurin inhibitor（cyclosporine or tacrolimus），apurine synthesis antagonist（azathioprine or mycophenolate mofetil），and prednisone is customary．

Subsequently，other drugs such as sirolimus may be substituted in the maintenance regimen for various reasons．Prophylaxis for pneumocystis jirovecii pneumonia is standard，and prophylaxis against cytomegalovirus（CMV） infection is prescribed in many protocols．The dose of cyclosporine or tacrolimus is adjusted by blood－level monitoring．Both are metabolized by the hepatic cytochrome P450 system，and interactions with medications that affect this pathway can significantly alter the clearance and blood levels of these key immunosuppressants．4

Routine management is designed to monitor the allograft，to regulate immunosuppressive therapy，and to detect problems or complications expeditiously．The techniques include periodic contact with a transplant nurse coordinator，appointments with a physician，chest radiographs，blood tests，spirometry，and bronchoscopy．Lung function rapidly improves and then stabilizes by 3—6 months after transplantation．Subsequently，the coefficient of variation in spirometric measurements is small，and a sustained decline of 10％—15％or more signals a potentially significant problem．5

Outcomes

The main sources of perioperative mortality include technical complications of the operation，primary graft dysfunction，and infections．Acute rejection and CMV infection are common problems in the first year，but neither is usually fatal．Beyond the first year，chronic rejection and non－CMV infections cause the majority of deaths．

Regardless of the disease，successful transplantation impressively restores cardiopulmonary function．After bilateral transplantation standard pulmonary function tests are typically normal；after single lung transplantation the remaining diseased lung typically contributes a mild abnormality．Formal exercise testing usually demonstrates some impairment in maximum work rate and maximum oxygen uptake，but few recipients report any limitation to activity．

Complications

Lung transplantation can be complicated by a variety of problems．Aside from those that are unique to transplantation，side effects and toxicities of the immunosuppressive medications can cause new medical problems or aggravate preexisting conditions．

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New Words and Phrases

therapeutic［,θerə'pjuːtɪk］a． 治疗的

nonmalignant［,nʌnmə'lɪɡnənt］a． 良性的

span［spæn］v． 包括；跨越

gamut［'ɡæmət］n． 全部；整个范围

idiopathic［,ɪdɪə'pæθɪk］a． 特发（性）的，自发（性）的

sarcoidosis［,sɑːkɒɪ'dəʊsɪs］n． 结节病

index［'ɪndeks］（［复］indices）n． 指数；指标

life expectancy［laɪfɪks'pektənsɪ］ 期望寿命，预期寿命

hepatitis B［hepə'taɪtɪs biː］ 乙型肝炎

antigenemia［æntɪdʒɪ'niːmɪə］n． 抗原血症

hepatitis C［hepə'taɪtɪs siː］ 丙型肝炎

irreversible［,ɪrɪ'vзːsəbl］a． 不可逆的

noncompliance［,nɒnkəm'plaɪəns］n． 不服从

aggravate［'æɡrəveɪt］v． （使）加剧；（使）恶化

ventilator［'ventɪleɪtə］n． 呼吸机

thoracic［θɔː'ræsɪk］a． 胸的，胸腔的

osteoporosis［,ɒstɪəʊpə'rəʊsɪs］n． 骨质疏松

cachexia［kə'keksɪə］n． 恶病质

allocation［æləʊ'keɪʃən］n． 分配；配给

compatibility［kəm,pætɪ'bɪlɪtɪ］n． 适合性，相容性

latitude［'lætɪtjuːd］n． 范围，自由度

algorithm［'ælɡərɪðəm］n． 运算法则；规则系统

parameter［pə'ræmɪtə］n． 参数

preclude［prɪ'kluːd］v． 排除

anomaly［ə'nɒməlɪ］n． 异常

conjunction［kən'dʒʌŋkʃən］n． 结合；关联；连接

concomitant［kən'kɒmɪtənt］a． 相伴的；伴行的；伴发的

buffer［'bʌfə］n． 缓冲；缓冲剂

cadaveric［kə'dævərɪk］a． 尸体的

lobectomy［ləʊ'bektəmɪ］n． 叶切除术

globulin［'ɡlɒbjʊlɪn］n． 球蛋白

purine［'pjʊrɪn］n． 嘌呤

mycophenolate mofetil 霉酚酸酯

prednisone［'prednɪsəʊn］n． 泼尼松

prophylaxis［prɒfɪ'læksɪs］n． 预防

pneumocystis jirovecii pneumonia 金罗维氏肺孢子虫肺炎

protocol［'prəʊtəkɒl］n． 方案，流程

cytochrome［'saɪtəkrəʊm］n． 细胞色素

immunosuppressant［,ɪmjuːnəʊsə'presənt］n． 免疫抑制剂

expeditiously［,ekspɪ'dɪʃəslɪ］ad． 迅速地

spirometry［spaɪə'rɒmɪtrɪ］n． 肺（活）量测定法，呼吸量测定法

bronchoscopy［brɒŋ'kɒskəpɪ］n． 支气管镜检查

coefficient［kəʊɪ'fɪʃənt］n． 系数

spirometric［spaɪrəʊ'metrɪk］a． 肺（活）量测定的；肺活量计的

Notes

1．Other problems that might increase the risk of complications or might be aggravated by the posttransplantation medical regimen constitute relative contraindications．

参考译文：其他可能增加并发症风险或移植后的医疗方案可能使病情加重的情况都是相对禁忌证。

句中other problems是主语，指前文中提到的other typical exclusions （其他典型的禁忌证）；constitute是谓语，意为“构成，是”。that引导定语从句，修饰other problems。

2．Heart－lung transplantation is obligatory for Eisenmenger syndrome with complex anomalies that cannot be readily repaired in conjunction with lung transplantation and for concomitant end－stage lung and heart disease．

参考译文：伴有复杂性异常且进行肺移植不易修复的艾森曼格综合征和伴发终末期心肺疾病的患者都必须进行心肺移植。

句中obligatory意为“义务的，必须的”，readily意为“容易地”，in conjunction with意为“连同，共同”，concomitant意为“相伴的，伴发的”。for Eisenmenger syndrome和for concomitant end－stage lung and heart disease是并列结构，做主句的状语；with complex anomalies是介词短语，做定语，修饰Eisenmenger syndrome；that引导的定语从句修饰complex anomalies，in conjunction with是介词短语，做从句状语。

艾森曼格综合征（Eisenmenger syndrome）是一组先天性心脏病发展列后期的表现。房室间隔缺损和动脉导管未闭等先天性心脏病，原来为左向右分流，由于进行性肺动脉高压发展至器质性肺动脉阻塞性病变，出现右向左分流，表现出皮肤黏膜从无发绀发展至有发绀时，即称为艾森曼格综合征。

3．In recipients with COPD andα1－antitrypsin deficiency emphysema，survival has been significantly better after bilateral transplantation，but there has not been a significant difference in survival between the two procedures for other diseases．

参考译文：慢性阻塞性肺病和α1抗胰蛋白酶缺乏的肺气肿患者进行双肺移植后生存时间明显延长，但其他疾病患者采取这两种手术（双肺和单肺移植），生存时间无显著差异。

句中survival has been significantly better指生存时间明显延长；two procedures指两种手术（双肺和单肺移植）。

4．The dose of cyclosporine or tacrolimus is adjusted by blood－level monitoring． Both are metabolized by the hepatic cytochrome P450 system，and interactions with medications that affect this pathway can significantly alter the clearance and blood levels of these key immunosuppressants．

参考译文：依据检测的血药浓度调整环孢素或他克莫司的剂量。两者都是由肝细胞色素P450系统代谢，其与影响这一代谢的药物相互作用，可以显著地改变这些重要的免疫抑制剂的血药清除率和血药浓度。

Both指上句中提到的cyclosporine和tacrolimus两种药物；pathway指metabolized by the hepatic cytochrome P450 system。clearance意为“清除率，廓清率”；blood level此处意为“血药浓度”。Both are metabolized．．．和interactions with medications that．．．can significantly alter．．．是由and连接的并列句；后一分句中interactions做主语，alter做谓语，意为“相互作用改变……”；with medications是介词短语修饰主语；that引导的定语从句修饰先行词medications。

5．Lung function rapidly improves and then stabilizes by 3—6 months after transplantation．Subsequently，the coefficient of variation in spirometric measurements is small，and a sustained decline of 10％—15％or more signals a potentially significant problem．

参考译文：移植后肺功能迅速改善，到3～6个月时趋于稳定。随后的肺（活）量测定变异如果系数很小，并且持续下降10％～15％或更多，就表明存在潜在的严重问题。

句中the coefficient of variation in spirometric measurements is small和a sustained decline of 10％—15％ or more signals a potentially significant problem是由and连接的并列句；后一分句中a sustained decline of 10％—15％or more是主语，signal做谓语，意为“发信号，表明”；the coefficient of variation意为“变异系数”。

Exercises

Ⅰ．Answer the following questions．

1．Can you give a general line of the present situation about the therapeutic consideration of lung transplantation worldwide？

2．Are patients supposed to obtain the opportunity for lung transplantation if they have clinically and physiologically severe lung disease but in reasonably good health？

3．What is your idea about waiting list and organ allocation？

4．To what indications is bilateral lung or heart－lung transplantation applied？

5．How is the posttransplantation management performed so as to guarantee the expected greater survivals in the lung transplantation？

Ⅱ．Decide whether the following statements are True or False．

1．Sarcoidosis and bronchiectasis are not common lung diseases，but they constitute the indications for lung transplantation．

2．The potential impact of relative contraindications of lung transplantation needn't to be considered in clinical context to determine an individual candidate's suitability for transplantation．

3．Priority of lung transplantation is determined by a lung allocation score that weighs both the patient's position on the waiting list and the likelihood of survival after transplantation．

4．Bilateral transplantation is mandatory for bronchiectasis and cor pulmonale because right ventricular function will recover when pulmonary vascular afterload is normalized by lung transplantation．

5．The main sources of perioperative mortality include technical complications of the operation，primary graft dysfunction，acute rejection and CMV infection．