C disease among whites [l, 21. Until recently, patients

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1 Double-Lung Transplantation for Cystic Fibrosis Hani Shennib, MD, Michel Noirclerc, MD, Pierre Ernst, MD, Dominique Metras, MD, David S. Mulder, MD, Roger Giudicelli, MD, Frangois Lebel, MD, Jean-Frangois Dumon, MD, and the Cystic Fibrosis Transplant Study Group The Joint Marseille-Montreal Lung Transplant Program, Thoracic Surgery Departments, Ste-Marguerite Hospital, Marseille, France, and The Montreal General Hospital, Montreal, Quebec, Canada One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that doublelung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors. (Ann Thorac Surg 1992;54:27-32) ystic fibrosis is the most common lethal genetic C disease among whites [l, 21. Until recently, patients with end-stage lung disease, despite all the advances in their medical care, were given palliative management once respiratory failure ensued and became evidently irreversible. Today, with the advent of heart-lung transplantation, many of these patients can be offered a chance to survive longer and with a better quality of life. Reports from the Harefield and Papworth Hospitals in Britain indicate that an actuarial survival that exceeds 70% can be expected after heart-lung transplantation for cystic fibrosis patients [3, 41. Pulmonary function and overall performance status of heart-lung transplant recipients were found to be superior to those before transplantation. Isolated single-lung transplantation was reintroduced successfully by the Toronto Group in This proved that lung units can function efficiently without an accessory new heart. In November 1986, en bloc double-lung transplantation was performed by the same group, and 16 months later, its role was expanded further by successful transplantation in 2 cystic fibrosis patients around the same time in Marseille and Toronto. Since then, with the continuous interest in expanding the role of isolated lung transplantation as an alternative to heart-lung transplantation, questions such as facility and safety of the technique of double-lung transplantation have emerged as serious deterrents for surgeons who have had better success with heart-lung transplantation. Nevertheless, the use of double-lung transplantation continues to ex- Presented at the Twenty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Feb 18-20, Address reprint requests to Dr Shennib, Joint Marseille-Montreal Lung Transplant Program, 1650 Cedar Ave, Rm 9828 LH, Montreal, Que, Canada H3G 1A4. pand mostly due to (1) local donor pool restrictions rendering isolated lung allografts more available than complete heart-lung blocks, (2) improvements in the technique of double-lung transplantation, most importantly, replacement of the tracheal anastomosis with bilateral bronchial ones, and (3) the reallocation of extrainees of the Toronto Lung Transplant Program who went on to develop isolated lung transplant centers elsewhere. Due to the heterogeneity of diseases in recipient pools and the, as yet, limited experience with double-lung transplantation, it is difficult to identify peculiarities and success rates for specific illnesses such as bronchiectasis and cystic fibrosis. The Cystic Fibrosis Transplant Study Group was initiated by the Montreal and Marseille Transplant Centers in response to the need for the development of an academic group whose responsibility would be to accumulate data, design studies, and report on transplantation for cystic fibrosis. This was thought to be necessary as cystic fibrosis transplant-related issues go beyond the procedure itself and include (1) identification of specific preoperative selection criteria and comprehension of the unusual patterns of disease progression, (2) recognition of the risks of development of certain infections and management of diabetes and drug toxicities postoperatively, (3) development of preoperative and postoperative registries, and (4) establishing rapport with referring cystic fibrosis clinics. This article, the first by the group, addresses the current experience with the procedure of double-lung transplantation for patients with cystic fibrosis. The present report is based on a retrospective review of our early experience with isolated double-lung transplantation during its evolution from en bloc tracheal to en bloc double bronchial anastomoses and finally to the separate sequential technique by The Society of Thoracic Surgeons /92/$5.00

2 28 SHENNIB ET AL Ann Thorac Surg 1992;54:27-32 Material and Methods Preoperative Evaluation and Care One hundred thirty-eight cystic fibrosis patients with end-stage lung disease were referred to our Cystic Fibrosis Transplant Centers during the period between April 1988 and April Referrals were based on the concern by treating physicians that their patients were terminally ill and that life expectancy would not exceed a year. No age, functional, socioeconomic, or geographical limitations were put before referral; however, referring physicians were kept informed of the criteria of acceptance within our programs and were encouraged to participate in formulating acceptance criteria in general and to attend Cystic Fibrosis Transplantation Committee meetings. One hundred twenty patients were accepted as candidates for double-lung transplantation as they fulfilled the following criteria: (1) progressive, rapid or steady decline in general and pulmonary function, so that the impression of the Cystic Fibrosis Transplantation Committee members was that life expectancy was less than 1 year, (2) satisfactory psychosocial background or a conviction of the committee members that psychosocial stability could be achieved before actual transplantation and maintained thereafter, (3) lack of other irreversible systemic organ failure, ie, cardiac, renal, hepatic, or hematologic. In general, a guarded 1-year life expectancy was based on progressive weight loss despite maximal nutritional support, increase in frequency and duration of hospitalization, and rapid reversible decline in forced expiratory volume and forced vital capacity, usually less than 30% predicted. We did not exclude patients with multiresistant organisms, mycobacterial, or fungal infections. Patients on mechanical ventilation were considered acceptable for transplantation provided no other organ failure was detected. Patients accepted for transplantation were instructed to remain at their residences provided a mechanism of transportation had been arranged to guarantee arrival to our centers within a maximum of 2 hours. Of the 120 patients accepted for transplantation, 25 died awaiting transplantation 1 to 61 days after their registration with organ retrieval networks. Patients awaiting lung transplantation actively participated in a rehabilitation and nutritional program tailored to the patients' own abilities and needs. When possible rehabilitation included respiratory and skeletal muscle strengthening exercises and incremental aerobic training. Nutritional support commenced with a trial of oral supplements and progressed to nasogastric gavage or feeding gastrostomy if the first method was deemed inadequate. Operative Techniques Twenty-five patients with cystic fibrosis underwent transplantation during the period between April 1988 and April The first 2 patients received double-lung transplants en bloc with a tracheal anastomosis, one main pulmonary artery anastomosis, and one posterior left atrial anastomosis. Subsequently, the procedure was modified to replace the tracheal anastomosis with two separate bronchial anastomoses in the next 15 patients. As of May 1990, all double-lung transplantations were performed with the sequential separate lung techniques using two bronchial, two pulmonary artery, and two lateral left atrial anastomoses. Eight cystic fibrosis patients received lung transplants using this technique. Cardiopulmonary bypass was used in all patients receiving en bloc double lungs and in 6 of 8 receiving sequential lungs. Lung allografts were preserved with modified Euro- Collins solution. No prostanoids were used before or during flushing of the preservation solution. In the current technique used, the patient is given aggressive physiotherapy and aerosolized bronchodilators before transfer to the operating room. The patient is given general anesthesia and ventilated with a left-sided double-lumen tube. The patient is positioned supine with both arms suspended above the head. A transverse transsternal incision is made across t'he fourth or fifth intercostal space. We prefer the fourth intercostal space in patients who have extensive disease in the upper lobes with the hila retracted cephalad. The right lung is deflated, and once the oxygen saturation and the hemodynamic status of the patient are ascertained io be stable, dissection is carried out to complete the pneumonectomy on the right side. The left side is assessed without much manipulation to obtain an estimate of the duration required for completing the left pneumonectomy. Once the donor lungs have arrived, the right lung is separated and prepared for implantation while the left is returned with the left bronchus stapled into the ice box. A right single-lung transplantation is performed as previously described. If the expected mobilization and implantation of the left lung is estimated not to exceed 1% hours, the left hilum is clamped and a period of observation is allowed to ascertain adequate right lung function and hemodynamic stability when the circulation is directed entirely through the new lung. A left pneumonectomy is completed and the left single-lung transplantation is then performed. If, however, the patient is hemodynamically unstable or the expected dissection and implanlation time for the left lung exceeds 1% hours, cardiopulmonary bypass is immediately instated through the right atrium and ascending aorta. We have been satisfied with the use of modified Euro- Collins solution, 30 ml/kg, administered at 4 C with the lungs mechanically ventilated at a higher tidal volume of 25 ml/kg. The lungs are usually stored in a hyperinflated state. Postoperative Managemen f Immunosuppression consisted of cyclosporine, azothioprine, and steroids. Early after transplantation steroids were avoided if possible, antilymphocytic sera were administered for the first 7 to 14 days, and cyclosporine was administered intravenously. Routine transbronchial biopsies were performed at 1 and 4 weeks, 3, 6, 9, and 12 months, and every 6 to 12 months thereafter. Patients were entered in a posttransplantation rehabilitation program and carried a pocket-size daily agenda to register daily temperatures, pulmonary flow rates, immunosuppression taken, and subjective sense of well-being on a

3 Ann Thorac Surg 1992;54:2732 SHENNIB ET AL 29 visual analogue scale. Cyclosporine whole blood levels, dosage, and peripheral blood white cell count were also recorded. This agenda served as a portable medical file for the use of patients and physicians. It also allowed us to determine patients' level of compliance. < 68% Results Of the 25 patients who underwent double-lung transplantation, 13 were female and 12 were male. Their mean age was 28 years (range, 7 to 34 years). Transplanted patients had a mean average Schwamann score of 42.8 and a mean percentage ideal body weight of 76% (range, 58.5% to 91.9%). Most patients had an elevated arterial carbon dioxide level before transplantation (mean, 66.6 mm Hg) and were hypoxic (mean arterial oxygen tension, 53.6 mm Hg) requiring continuous use of oxygen therapy. Sputum bacterial cultures and sensitivities were well documented in 23 patients. Nineteen had Pseudomonas species sensitive to one or more antibiotics, whereas 4 were resistant to all known single or combination antibiotics. Two patients had Pseudomonas cepacia. Four patients were found to grow mycobacteria: preoperatively from sputum samples in 2 patients and postoperatively from cultured lung tissue or hilar lymph nodes in 2 other patients. Six patients grew fungus from their sputum or lung tissue: 4 had Aspergillus fumigatus and 2 had extensive Candida albicans growth. All patients were covered with specific antibiotic therapy or, when resistant, with aerosolized colistin or tobramycin and a combination of two intravenous antipseudomonal drugs perioperatively and postoperatively. Amphotericin, 0.2 mgkg per day, was given prophylactically in all our patients for a period of 1 to 4 weeks. Only 1 of 4 patients with mycobacterial infection received a 4-week course of ceftazidimel clindamycin for Mycobacterium chelonei grown from hilar lymph nodes at the resection margins. None of our patients had recurrence or relapse of the primary infection in the lung allografts. None of the deaths could be attributed to the nature of infections before transplantation. Eighteen patients were breathing spontaneously before operation, whereas 7 patients were mechanically ventilated. Twelve of the 18 spontaneously breathing patients (67%) and 5 of the 7 mechanically ventilated patients (71%) were alive at 3 months after transplantation. Lung allografts were subjected to an average of 4:24 hours of ischemic time (range, 1:16 to 9:15 hours). Cardiopulmonary bypass was used in 23 patients (mean time, 3:51 hours; range, 1:30 to 6:15 hours). Two patients with moderate pleural adhesions underwent sequential lung transplantation without using cardiopulmonary bypass. The overall intraoperative mortality was 16%. Two of the 15 patients who underwent the en bloc procedure and 2 of the 8 patients who received sequential transplants died intraoperatively. All 4 patients had extensive adhesions and massive bleeding requiring transfusion of more than 10 units of blood. Adhesions were present throughout the pleural cavity but were much denser in the region of the posterior mediastinum and hilum. Actuarial sur- $? 10 0 I.,.,.,, I, OR 1 month 3 months 6 months 12 months Fig 1. Actuarial survival early after double-lung transplantation for cystic fibrosis. vival, shown in Figure 1, was 76%, 68%, 64%, and 64% at 1, 3, 6, and 12 months. At 2 years, survival was 56%. Of 11 patients who have been followed up for more than 1 year, 9 had good lung function and normal activity whereas 2 had development of obliterative bronchiolitis. At 1 month, 19 patients had had 17 episodes of rejection and 13 episodes of infection. By 6 months, the total number of episodes of rejection was 21 and the number of infection episodes was 17. During the next 6 months, only 4 episodes of rejection were reported. Rejection was determined by a transbronchial biopsy finding of rejection or clinical and radiologic response to pulse high-dose steroid therapy. This information should be interpreted with caution as only 11 patients have now completed the 1-year follow-up. Airway complications occurred in 5 patients: partial dehiscence of the bronchial anastomosis developed in 1, stenosis at the anastomotic site in 2, and diffuse bronchomalacia around the bronchial anastomosis in 2 others. All responded well to laser stricturoplasty, stent insertion, or both, with recovery of lung function. Comment Until recently, heart-lung transplantation was the only surgical procedure available for the treatment of end-stage septic lung disease. Single-lung transplantation in the setting of bilateral lung infection is thought to carry formidable risks by leaving one infected lung behind. Removal of both lungs and implanting only one has been entertained; however, there is concern for the development of empyema in the empty hemithorax. Double-lung transplantation was described by the Toronto Lung Transplant Group in 1987, initially for emphysema and subsequently for other lung diseases including bronchiectasis. The first two successful double-lung transplantations for cystic fibrosis were performed in April 1988 by the Marseille and Toronto Groups. Both transplantations were done using the old technique of tracheal anastomosis. A very high incidence of airway complications related to the tracheal anastomosis necessitated a revision of the technique of double-lung transplantation. Soon after,

4 30 SHENNIB ET AL Ann Thorac Surg 1992;54:27-32 Noirclerc and associates [5] described the technique of separate bronchial anastomosis. With minor alterations in the suture techniques used, this has been the anastomosis of choice for all double-lung transplantations today. In 1989, both the Toronto and St. Louis groups applied the technique of single-lung transplantation to remove and implant two separate lungs [6]. This proved to be valuable in reducing the need for cardiopulmonary bypass, a procedure that, when prolonged, is associated with an increased risk of operative bleeding. Furthermore, application of the transverse transsternal incision, rather than the vertical sternotomy, has facilitated bilateral separate lung implantation by better visualizing the hila and posterior mediastinum. Extensive thick posterior mediastinal adhesions and the presence of large systemic arterial collateral vessels contributed to the difficulty of pneumonectomy and massive bleeding encountered in many of our patients. Avoiding cardiopulmonary bypass would have been ideal. Unfortunately, it is our experience that it is in those patients with massive adhesions that retraction on the mediastinum in the course of the difficult dissection will lead to hemodynamic instability and cardiac arrhythmia necessitating frequent use of cardiopulmonary bypass. Furthermore, direction of the whole circulation, abruptly and for a long interval, to the newly implanted lung and until the second allograft is complete may result in exaggerated reperfusion injury. In fact, we have frequently observed that the first implanted lung, which has a shorter ischemic time, will show more clinical and radiologic signs of reperfusion injury than the second implanted lung with the longer ischemic time when no cardiopulmonary bypass is used. We have since adopted a strategy of assessing the extent of pleural and mediastinal adhesions and estimating the time required for pneumonectomy and implantation of the second lung. If this appears likely to exceed 1% hours, cardiopulmonary bypass is instated after completion of the first transplant and before the second pneumonectomy. In essence, we aim to protect the newly implanted lung and reduce cardiopulmonary bypass time. Postoperatively, patients with cystic fibrosis who are recipients of double-lung transplants are subject to the same complications as patients with other end-stage lung disease. Rejection and infection are frequent during the first months and decrease in incidence by 6 months after transplantation. We could not detect a difference in the infectious complications between patients who had resistant Pseudomonus bacteria (including cepuciu species), mycobacteria, or fungus and those who did not have the organisms cultured from their lungs. Similarly, no difference in survival was noted between patients who underwent transplantation while mechanically ventilated or spontaneously breathing. Although our experience remains small, such early findings would suggest that cystic fibrosis patients with difficult infection or colonization and ventilator dependency should not be denied the chance of a transplantation. As some patients will continue to harbor Aspergillus and Cundida in their upper airway after transplantation, we have adopted the use of amphotericin prophylactically on all our patients; whether this is justifiable or not is yet to be determined. Aggressive preoperative nutritional and physiotherapy support to maintain the general and respiratory muscle function at a reasonable level is of utmost iimportance if such patients are to be carried safely through transplantation to postoperative ventilatory independence. Airway complications continue to be a leading cause of morbidity in recipients of isolated lung transplants. It may be that our preservation methlods are inadequate to provide protection of the airway, particularly in regions more distant from lung parenchyma. The administration of steroids early after transplantation, something we have avoided in our early experience, may help minimize rather than increase the risk of airway complications, perhaps by downstaging the immunological effects of ischemia and early rejection [7]. Methods aimed at preserving the integrity of airway during procurement have not yet been addressed and would be a welcome contribution to the science of lung transplantation. Management of localized stenosis and malacia at the bronchial anastomosis by laser therapy and bronchial stenting have made it possible to manage most anastomotic complications. The postoperative management of patients with cystic fibrosis who are recipients of double-lung transplantation is quite challenging. Maintenance of therapeutic blood levels of cyclosporine is difficullt. Most patients are started on oral cyclosporine with the simultaneous administration of their usual doses of pancreatic enzymes. If high doses of cyclosporine are needed without achieving the therapeutic blood levels, we then administer diltiazem in increasing doses up to 90 mg iwice daily with the cyclosporine. Not only have we achieved therapeutic cyclosporine blood levels and reduction of the dosage of cyclosporine administered, we have also noticed that the blood levels become more stable over long periods of observation. Insulin-dependent diabetes mellitus will develop in almost all patients immediately after transplantation as a result of stress and administration of steroids. Fortunately, most patients will require minimal or no insulin once they have reached the 6-nnonths point when they are on minimal doses of prednisone. In conclusion, double-lung transplantation is a viable option for the treatment of cystic fibrosis patients with end-stage lung disease. Early inorbidity after transplantation continues to be high, with a one in three chance of death by the end of the first year. Current improvements in operative technique with the use of an incision and the sequential technique and advances in immunosuppression to minimize rejection and related infections should lead to improvement in results. We would like to acknowledge the assistance of Dr Riad Adoumie, Cyril Serrick, and Anna Vaccaro in the preparation of the manuscript. The Cystic Fibrosis Transplant Group consists of: Marseille: Dr Michel Noirclerc, surgeon; Dr Jean-Fransois Dumon, respirologist; Dr Roger Giudicelli, surgeon; Dr Dominique Metras, surgeon; Dr Jean-Pierre Chazalette, pediatric respirologist; Dr Lolette Garbe, pathologist; Dr Jean-Michel Triglia, otorhinolaryngologist; Dr Jean-Pierre Aufray, anesthesiahitensivist; and Dr Alain Bar-

5 Ann Thorac Surg 1992;54:27-32 SHENNIB ET AL 31 thelemy, anesthesiahntensivist; Montreal: Dr Hani Shennib, surgeon; Dr Pierre Ernst, respirologist; Dr David Mulder, surgeon; Dr FranGois Lebel, microbiologist; Dr Rick Fraser, anatomopathologist; Dr Andre Lamarre, pediatric respirologist; Dr Richard Gauthier, respirologist; Dr Alphonse Jeanneret, respirologist; and Dr Fransoise Chagnon, otorhinolaryngologist. References 1. Colten HR, Wilson JD, Brawnwald E, et al. Cystic fibrosis. In: Harrison s principles of internal medicine, 12th ed. New York McGraw-Hill, 1991: Scanlin TF. Cystic fibrosis. In: Fishman AP, ed. Pulmonary diseases and disorders, 2nd ed. New York: McGraw-Hill, 1987: Jones L, Higenbottam T, Wallwork J. Successful heart-lung transplantation for CF. Chest 1988;93: Yacoub MH, Banner NR, Khaghani A, et al. Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation. J Heart Transplant 1990;9: Noirclerc MJ, Metras D, Vaillant A, et al. Bilateral bronchial anastomosis in double lung and heart-lung transplantation. Eur J Cardiothorac Surg 1990; Pasque MK, Cooper JD, Kaiser LR, et al. Improved technique for bilateral lung transplantation: rationale and initial clinical experience. Ann Thorac Surg 1990;49: Nguyen D, Mulder DS, Shennib H. Warm ischemia induces alteration in lung immune cell functions. J Thorac Cardiovasc Surg 1991;101:103&6. DISCUSSION DR MICHAEL K. PASQUE (St. Louis, MO): I would like to congratulate Dr Shennib and associates for the excellent results they have obtained in the application of lung transplantation to the cystic fibrosis patient population. With the possible exception of patients with end-stage pulmonary hypertension, cystic fibrosis patients represent the most challenging subset of patients who may benefit from lung transplantation. The absolute need for total lung replacement in this group of patients led initially to the application of heart-lung transplantation. Subsequent development and application of en bloc doublelung transplantation was plagued by difficulties unique to cystic fibrosis patients. Specifically, perioperative hemorrhage related to dense pleural adhesions and chronically inflamed mediastinal structures became life-threatening when combined with the heparinization and the coagulopathy associated with cardiopulmonary bypass. Poor access to these posterior structures through the median sternotomy incision made matters worse. The mandatory cardiac ischemia required during the single left atrial anastamosis was not well tolerated by these cystic fibrosis hearts. Our dissatisfaction with the results of our initial application of en bloc double-lung transplantation for cystic fibrosis at Washington University led us to a full-scale attempt to simplify this procedure with the specific characteristics of the cystic fibrosis patients in mind. The resulting bilateral sequential lung transplant procedure has eliminated the need for cardiopulmonary bypass in the majority of cystic fibrosis patients in our experience, thus eliminating the hemorrhage related to heparinization and the associated pump coagulopathy. It has essentially eliminated postoperative myocardial depression by eliminating the single left atrial anastomosis and the resulting need for myocardial ischemia. The bilateral bronchial anastomoses have eliminated the need for the extensive mediastinal dissection required for recipient airway removal and the subsequent tracheal anastomosis and have improved airway healing. The bilateral thoracosternotomy gives excellent exposure for implantation and control of hemorrhage. The result has been a marked decrease in the perioperative morbidity and mortality, with 5 of our last 6 patients leaving the hospital in excellent condition. I would be interested in Shennib and associates views on several key issues. First, what do they believe should be the role of each of the lung transplant options, including heart-lung transplantation, the en bloc double bronchial method, and the bilateral sequential lung transplant in the cystic fibrosis patient population? Second, we have avoided cardiopulmonary bypass in all but 1 of our 6 cystic fibrosis patients who have undergone the bilateral sequential technique by aggressive anesthetic management, including judicious airway suctioning, aggressive use of inotropes and specific pulmonary arterial vasodilators, and close operative monitoring of biventricular function by transesophageal echocardiography. It would be informative to know the specific indications that led to the use of cardiopulmonary bypass in three-quarters of the bilateral sequential patients presented in their series. Finally, although Shennib and associates specifically mentioned that there were few criteria for exclusion of cystic fibrosis patients from transplantation, they did not specifically describe their inclusion criteria. In other words, when is the cystic fibrosis patient sick enough to be a candidate for transplantation? What criteria are critical in their decision? How hypoxic must the patient be, how many infectious episodes must be sustained, and how debilitated should the patient be? DR THOMAS M. EGAN (Chapel Hill, NC): I rise to congratulate Dr Shennib and associates on their excellent results. This represents the largest series to date of isolated lung transplantation for cystic fibrosis, and for those of us who have had experience with this problem, these patients clearly represent one of the more challenging groups of patients for lung transplantation. I had the pleasure of visiting Dr Noirclerc in Marseille a year ago, and he obliged me by performing a double-lung transplantation on a patient with cystic fibrosis during my stay. At the University of North Carolina in Chapel Hill, since October of 1990 we have performed four double-lung transplantations in patients with cystic fibrosis, all using the bilateral approach so well described by Dr Kaiser 2 days ago. One of these patients required a redo transplantation at 7 days postoperatively for thrombosis of the initial left lung graft. All 4 patients have survived and all have been discharged home off oxygen and fully ambulatory. Because our center is an adult cystic fibrosis center, we have had experience with 18 referrals to date for patients with cystic fibrosis; 4 have undergone transplantation, and 6 are listed or waiting. The forced vital capacity of the transplanted and listed patients is 40% predicted (mean) with a range of 29% to 52%. The forced expiratory volume in 1 second in the transplanted and listed patients is 20% of predicted. I too would like Dr Shennib and associates to comment on their inclusion criteria, and in particular, how do they decide in whom to perform transplantation? With reference to airway complications and the incidence of bronchomalacia, could they comment as well on the change in their technique and whether that has had an influence on airway complications?

6 32 SHENNIB ET AL Ann Thorac Surg 1992;54:2732 DR SHENNIB: I would like to thank Drs Pasque and Egan for their kind remarks. In regard to the first question of cardiopulmonary bypass, I do not think the purpose should be to avoid cardiopulmonary bypass. I think the purpose is to reduce the duration of time on cardiopulmonary bypass. We have seen quite frequently at the time of the operation that there is quite a high incidence of intraoperative arrhythmias due to handling of thc hilum and the maneuvers that you are required to do on and of one lung of ventilation. Indeed, we were able to perform trans plantation on 2 patients completely off bypass, but that does no mean that we will try routinely to do it totally off bypass. I think again, as I mentioned, the purpose is to minimize the &r-+inn Q cardiopulmonary bypass. To do it totally off bypass I purpose. In regard to the assessment of patients, how we select ou patients, we have a committee that meets regularly every time,. cystic fibrosis patient is presented. This committee is made of four cystic fibrosis clinic directors who have quite a lot of experience in cystic fibrosis patients, in addition to the cystic fibrosis transplantation team that we have, and we go through all the criteria that have led the patient to be presented to us. Primarily these are repeated admissions to the hospital due to recurrent infections, decline in the overall status of the patient, including loss of weight despite maximum nutritional support, and the most important of all is the increase in the arterial carbon dioxide tension in those patients. The question of hemoptysis is important, but we have never actually had to accept a patient solely for the purpose of managing hemoptysis. In regard to the last question as to whether the incidence of airway complications is different between sequential lungs or en bloc double bronchial anastomoses, we have not seen a difference between the incidence of airway complications when we compared the two groups. In fact, the bronchial anastomoses were done exactly the same way.