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Right arrow Lung - transplantation

Eur J Cardiothorac Surg 2002;22:602-609
© 2002 Elsevier Science NL

Long term results of lung transplantation for cystic fibrosis

T.M. Egan*, F.C. Detterbeck, M.R. Mill, M.S. Bleiweis, R. Aris, L. Paradowski, G. Retsch-Bogart, B.S. Mueller

Division of Cardiothoracic Surgery, Department of Surgery, University of North Carolina at Chapel Hill, 108 Burnett–Womack Building, UNC, Chapel Hill, NC 27599-7065, USA

Received 18 September 2001; received in revised form 26 April 2002; accepted 17 June 2002.

* Corresponding author. Tel.: +1-919-966-3381; fax: +1-919-966-3475
e-mail: ltxtme{at}med.unc.edu


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 References
 
Objectives: We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. Methods: One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan–Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. Results: Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. Conclusions: DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Key Words: Lung transplant • Cystic fibrosis • Burkholderia cepacia • Lung retransplant • Bilateral lobe transplant


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Discussion
 References
 
As candidates for lung transplantation, cystic fibrosis (CF) patients pose daunting challenges for transplant surgeons. They are invariably underweight; many have glucose intolerance and abnormal liver function. Their airways and sinuses are colonized with large numbers of virulent organisms, often multiply- or pan-resistant. These organisms are impossible to eradicate prior to transplant. However, patients with CF are young and are often highly motivated to obtain a better health status. They are accustomed to complying with a complex medical regimen; thus, health care providers may be better able to judge the likelihood of compliance in patients with CF. Although CF is a multi-system disease, the extra-pulmonary disease ordinarily is not life threatening while respiratory failure is the cause of death in over 95% of CF patients [1]. During the 1990s, CF has become a major indication for lung transplant, accounting for half of all pediatric lung transplants and one-third of adult bilateral lung transplants reported to the Registry of the International Society for Heart and Lung Transplantation [2].

After over 10 years of experience with lung transplantation for CF patients, we chose to review our experience to determine if our earlier encouraging results were sustained [3], and to report our limited experience with bilateral lobe transplant (BLLTX) and retransplant in CF patients. Because many CF patients are young, and because lung transplantation is controversial in the face of colonization with some organisms, we analyzed the impact of age and presence of Burkholderia cepacia on outcome of lung transplantation for CF patients in our program. To determine where efforts to improve outcome might be most successful, we also analyzed causes of death.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Discussion
 References
 
All patients with CF, who underwent double lung transplant or BLLTX at University of North Carolina (UNC) Hospitals between October 1990 and July 2001 were included in the analysis. Data were retrieved from lung transplant patient files or transplant spreadsheets. Results were analyzed in August 2001. Kaplan–Meier survival was calculated and depicted graphically for the entire cohort and for different subsets using Statistica® software (Statsoft, Tulsa, Oklahoma, USA). Kaplan–Meier survival estimates were compared with Gehan's Wilcoxon test. Differences were considered significant if P<0.05.

2.1. Patient selection
A study by Kerem et al. [4] from the Hospital for Sick Children in Toronto has helped to identify predictors of mortality in CF patients, and has been useful to identify CF patients who stand to benefit from lung transplantation (LTX) with respect to survival. In Kerem's analysis, forced expiratory volume in 1 s (FEV1) less than 30% predicted was associated with a risk of mortality of 50% within 2 years in patients under the age of 18 years; risk of death was 40% in patients older than 18 years. If FEV1 was less than 20%, the risk of death within 2 years increased to 70% for young patients and 58% for adults. Risk was higher in females and in patients for whom the weight-for-height ratio was less than 70% predicted. Patients with a room air pO2 below 55 mmHg or pCO2 above 50 mmHg had a 2-year mortality risk that exceeded 50%. A history of reducing exercise tolerance, increasing requirements for hospitalization or intravenous antibiotic therapy, increasing need for supplemental oxygen, and difficulty in maintaining weight all portend a poor prognosis for CF patients. In our experience, mortality on the waiting list is associated with a significantly lower FEV1 than that for listed CF patients who survived long enough to be transplanted [5].

Prospective lung transplant candidates must be ambulatory and willing to participate in a pulmonary rehabilitation program. They must have the means to be able to return to our center for follow-up, and be able to comply with a complex medical regimen. Contraindications for transplant among CF patients at UNC are listed in Table 1. Although there is limited experience with combined liver and lung transplant at some centers to address the issue of liver dysfunction, it is difficult to promote this procedure in the US, given the current scarcity of lungs for transplant.


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  		Table 1. Contraindications to CF lung transplant

 
Diabetes mellitus is not an absolute contraindication because diabetes itself does not appear to adversely affect prognosis in CF patients. However, end organ involvement due to diabetes, such as renal failure or neuropathy, may have a substantial impact on outcome following transplantation. We have not excluded patients on the basis of nutritional parameters. Nutritional status has been shown to improve following lung transplantation, irrespective of the pretransplant diagnosis. Requirement for preoperative ventilation in CF patients has not been associated with increased perioperative risk in properly selected candidates, and thus is not considered an absolute contraindication [6,7]. However, increased preoperative debility likely impacts on the duration of postoperative ventilation, increasing cost and possibly the risk of pneumonia.

Patients colonized with B. cepacia have been reported to have an increased risk of adverse outcome following lung transplantation [8,9]. However, we have not considered this an absolute contraindication, but advise prospective candidates of the risk of a poorer outcome. We do not consider colonization with pan-resistant Pseudomonas, Aspergillus, or mycobacterial species to be a contraindication to transplant.

Indications for retransplant are the same as first time transplant. Unfortunately, many CF patients who develop end stage lung disease due to bronchiolitis obliterans syndrome (BOS) are not candidates for retransplant, due to renal dysfunction, or difficulties coping with the stress of transplant. However, if other organ systems are intact, we are willing to retransplant compliant patients who have developed terminal lung disease due to BOS because in our experience, prior thoracotomy has not impacted on lung transplant outcome.

2.2. Operative technique
2.2.1. Double lung transplant
The technique for double lung transplant has continued to evolve, from the ‘en bloc’ procedure to bilateral bronchial anastomoses, to the sequential technique through a clamshell incision, to sternal sparing bilateral anterior thoracotomies [10], which is our current technique of choice for lung replacement in CF patients.

The technique we employ has been described in detail elsewhere [11] and is summarized here. We begin the transplant procedure by orotracheal intubation with a large-bore, single-lumen endotracheal tube, followed by fiberoptic bronchoscopy, to aspirate as much purulent material as possible from the airways. This facilitates one lung ventilation, and avoidance of cardiopulmonary bypass. A left sided double lumen endotracheal tube is positioned. The chest is entered through anterior bilateral thoracotomies in the fifth or fourth interspace via a submammary skin incision. In the event of dense adhesions, sternal division affords better exposure. The first lung explanted is usually the right, unless the quantitative perfusion scan performed at listing indicates that there is a significant disparity in perfusion; if so, the least perfused lung is explanted first. Following recipient pneumonectomy, the airway and pleural space are irrigated with copious amounts of dilute betadine to reduce the amount of purulent material in the native airway and pleural space.

We prefer an end-to-end bronchial anastomosis, using a running monofilament polyglycolic acid suture (Maxon®, Sherwood-Davis and Geck, St. Louis, Missouri, USA) on the membranous portion and interrupted braided polyglycolic acid sutures (Dexon II®, Sherwood-Davis and Geck) on the cartilaginous portion. We abandoned omentopexy in light of reports that this does not appear to be necessary; instead, we buttress the bronchial anastomosis with peribronchial tissue from the lung to the recipient mediastinum. The vascular anastomoses are performed with running Prolene® (Ethicon, Somerville, NJ, USA). We generally use an everting mattress technique on the atrial cuff. Gradients across the pulmonary artery (PA) anastomoses are measured with a 25-gauge needle attached via high pressure tubing to a pressure transducer. After completion of the transplant, the double lumen tube is replaced with a single lumen tube, and bronchoscopy is performed again to inspect the airway anastomoses and aspirate any purulent material for culture.

Cardiopulmonary bypass is always available, and when instituted, aprotinin is utilized to minimize blood loss. Bypass is employed if patients do not tolerate one lung anesthesia due to right heart failure, inability to oxygenate, or the development of pulmonary edema. Ventilatory strategy during one lung ventilation is an attempt to maintain pH in a reasonable range (>7.2) and oxygen saturations above 90%. Pulmonary hypertension is treated with intravenous nitroglycerine. We have little experience with the use of nitric oxide in these patients.

Because CF patients tend to be of small stature, many prospective donors may be larger. This can result in a substantial size discrepancy between donor lung size and the size of the recipient thorax. We have performed ‘pneumoreduction procedures’ to deal with this size discrepancy by resection of donor lung tissue after completion of a transplant, which has safely allowed the use of larger donors in smaller recipients [12].

2.2.2. Bilateral lobe transplant
An alternative to double lung transplant is the use of lobes from two living donors [13]. We have employed bilateral lobe transplant (BLLTX) when CF lung transplant patients became so ill that survival on the list is unlikely. BLLTX requires two healthy donors of compatible blood type with no contraindications to thoracotomy who are taller than the intended recipient. It is sometimes difficult to identify two appropriate donors. The operation is performed on cardiopulmonary bypass, in a similar manner to double lung transplant. We usually transplant the left lower lobe first on full bypass, and then perform the right on partial bypass. On the right side, we anastomose the right lower lobe donor bronchus to the recipient bronchus intermedius, after closing the right upper lobe bronchus with a TA-30 stapler at the time of recipient pneumonectomy.

2.3. Immunosuppression
Our immunosuppression protocol consists of intravenous cyclosporine started in the operating room, azathioprine 2 mg/kg daily, and methylprednisolone 125 mg t.i.d. for the first day, followed by 0.5 mg/kg daily for the first month. Neoral® (Novartis, Basel, Switzerland) is used when gut function resumes. In patients who experience recurrent episodes of rejection, mycophenylate and tacrolimus are substituted for azathioprine and Neoral, respectively. Prednisone dose is tapered over 6–9 months to a baseline of 15 mg/day. By 1 year post-transplant, in patients who have had no episodes of rejection in the last 6 months, prednisone is administered at a dose of 10–15 mg every other day to reduce Cushingoid side effects. In the first 57 patients, University of Minnesota anti-lymphocyte globulin or Atgam® (Upjohn, Kalamazoo, Michigan, USA) was utilized as induction therapy.

2.4. Postoperative management
2.4.1. In hospital
Rigorous attention to airway clearance, adequate analgesia, and ambulation are essential to facilitate early extubation. Prophylactic antibiotics are administered for the first week and are tailored to antibiotic sensitivities of preoperative recipient and donor sputum cultures. In the absence of significant ischemia-reperfusion injury, we attempt to extubate patients within 24 h of completion of the procedure.

Postoperative ileus and gastric atony is common and may be related to intrathoracic vagal nerve injury. Thus, total parenteral nutrition is initiated early postoperatively, but feeding is via the enteral route when gut function resumes. Prevention of meconium ileus equivalent, or distal intestinal obstruction syndrome (DIOS), is necessary. Gastric bezoars are not uncommon. Chest tubes are removed when drainage is <100 ml/12 h, usually 10–14 days following transplant. If there are no other problems, patients are discharged from hospital after chest tubes are removed and pain control is adequate on oral agents.

We evaluated a program of cytomegalovirus (CMV) prophylaxis with 2 weeks of gancyclovir in all CMV positive recipients, but abandoned this when no benefit was established. However, we do treat CMV naive recipients with 4 weeks of intravenous gancyclovir and seven doses of Cytogam® (Medimmune, Gaithersburg, Maryland, USA) over 16 weeks.

Patients colonized with B. cepacia are now maintained on intravenous and inhaled antibiotics for at least 30 days following transplant.

2.4.2. Out patient
Lung transplant recipients participate in a program of increased aerobic exercise for 4–8 weeks after hospital discharge. Prophylactic medications include daily acyclovir, thrice weekly double strength Bactrim (trimethoprim sulfate 160 mg and sulfamethoxazole 800 mg), H2 receptor antagonists, and ADEK vitamins taken indefinitely. Oral Nystatin is administered until prednisone is reduced, or as needed. Osteopenia is frequently diagnosed pretransplant and is treated with Pamidronate or Fosamax. Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy is performed every 3 months for the first year, or when indicated, based on fever or reduction in FEV1. Communication of any new symptoms is encouraged and facilitated by frequent contact with nurse coordinators.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Discussion
 References
 
Between October 1990 and July 2001, 123 patients with CF have undergone 131 lung transplant procedures at UNC; 114 have had bilateral sequential lung transplants (DLTX) and nine have had BLLTX from living donors. Three patients had retransplant for acute graft failure and five had retransplant for BOS. Among DLTX recipients, ten deaths occurred within 30 days or during the transplant hospitalization; thus, operative survival is 91%. Median hospital stay for DLTX recipients has been 22 days (mean 29, range 0–129 days). Ischemic time averaged (mean±SEM) 311±6 min for the first implanted lung and 478±8 min for the second. Cardiopulmonary bypass was employed in 22 DLTX recipients and had no impact on 1-year survival. Size reduction procedures were performed on 14 DLTX recipients, consisting of: right middle lobectomy alone in one, with right upper lobe in one, with lingula wedge resection in six, with bilateral apical resections in one. Right middle lobe wedge resections were performed with lingula wedge in three, and right upper lobe wedge in one, lingula wedge alone in one and bilateral lung apices alone in one.

Actuarial survival for the DLTX and BLLTX recipients is depicted in Fig. 1 . At 1, 5, and 10 years following DLTX, actuarial survival is 81, 58, and 36%, respectively. Lobar transplants have had poorer results at UNC with only four of nine patients surviving to discharge, and three long-term survivors. Lower lobe volunteer donors were both parents (4), two brothers (2), father and uncle (1), cousins (1), and husband and husband's brother (1).



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  		Fig. 1. Actuarial survival of CF patients having bilateral lung transplant (solid line) vs. BLLTX (dashed line). Numbers in parentheses indicate number of recipients at risk for each subsequent year.

 
We have reported good results for CF patients on a ventilator at the time of transplant [7]. Outcome of ventilated CF patients is summarized in Table 2. Ventilated patients must have been evaluated and listed for transplant prior to onset of ventilatory assistance, and have other organ systems intact to remain candidates for lung transplant.


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  		Table 2. Outcome of ventilated CF patientsa

 
Twenty-one patients were colonized with B. cepacia at the time of DLTX. Actuarial survival of cepacia patients compared to non-cepacia patients is depicted in Fig. 2 . One-year actuarial survival for CF patients colonized with B. cepacia was 58% compared to 86% for CF patients who did not harbor this organism. However, not all deaths among the cepacia patients were directly attributable to this organism. Five of eight deaths within 1 year of transplant were clearly attributable to B. cepacia, with no additional cepacia-related deaths beyond 6 months of transplant.



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  		Fig. 2. Actuarial survival of 21 CF patients colonized with B. cepacia (dashed line) vs. 93 CF patients without B. cepacia (solid line). (P<0.006).

 
Because International Registry reports suggest a poorer outcome for pediatric lung transplant patients [2], we evaluated the impact of recipient age on outcome, both by univariate analysis of time to death with age as a continuous variable, and by comparing actuarial survival of 23 recipients age 19 and under, with 91 recipients age 20 and over (Fig. 3 ). There was no difference in survival probability for younger CF patients.



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  		Fig. 3. Actuarial survival of 23 CF patients aged 19 and under (dashed line) vs. 91 CF patients aged 20 and over (solid line) at the time of bilateral lung transplant.

 
Retransplantation for acute graft failure was undertaken in three CF patients with success in two; one patient succumbed due to repeated graft failure and was suspected of having an intra-abdominal source of sepsis, but permission for autopsy was refused. After a change in the United Network for Organ Sharing (UNOS) distribution algorithm, acute retransplantation is no longer readily available in the US. Retransplantation for BOS has been performed in five CF patients with an in-hospital survival of 80% and 1 year actuarial survival of 60% (Fig. 4 ). Only one of three long-term survivors succumbed from recurrent BOS. Two other patients died of fulminant pneumonia that was presumably viral in origin. Interval from first transplant and outcome of retransplant for BOS is depicted in Table 3.



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  		Fig. 4. Actuarial survival of first time CF bilateral lung transplant (solid line) vs. CF retransplant for BOS (dashed line). For retransplant patients, first transplant survival was censored at the time of retransplant.

 

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  		Table 3. Outcome of retransplanted CF patientsa

 
Following bilateral lung transplant, 53 CF patients have died. Cause of death is depicted in Fig. 5 and is analyzed according to the time following lung transplant: in hospital or within 30 days (n=9), within 1 year of transplant (n=11), or beyond 1 year (n=33). Infection dominates post-transplant causes of death immediately and during the first year. Two cases of presumably lethal graft failure were averted by urgent retransplant. Beyond the first year post-transplant, BOS has accounted for approximately half of the deaths among CF patients; five deaths attributable to BOS were presumably averted by retransplant for BOS, and only one of these patients eventually succumbed from BOS (Table 3).



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  		Fig. 5. Causes of death following double lung transplant. (a) In-hospital deaths or within 30 days (n=9): of six infectious deaths, four were due to B. cepacia, one fungal and one Pseudomonas. (b) Within 1 year of transplant (n=11): of five infectious deaths, three were viral (one CMV), one was due to B. cepacia, and one fungal. Of four BOS deaths, non-compliance played a role in two. (c) Beyond 1 year of transplant (n=33): non-compliance contributed to three of 17 BOS deaths. BOS contributed to two infectious deaths. Three cancer deaths were attributed to PTLD [2] and esophageal cancer [1].

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
References
 
Although the early North American experience with heart–lung transplants for CF was discouraging [14], results from the UK (Harefield and Cambridge) were much better [15,16]. Double lung transplant was first successfully applied to patients with CF at the University of Toronto [17]. The 1-year actuarial survival in this cohort was 59% less than that achieved for patients with other diagnoses. The poorer outcome for patients with CF was attributed to the high incidence of B. cepacia in their patients [8]. As more experience accrued, results with lung transplant for CF have improved, with 1-year survival in excess of 80% reported at some centers [18,19].

Although immunosuppressive protocols may not increase the risk of infection with Pseudomonas or Staphylococcus aureus species, fungal infections (such as Aspergillus) and mycobacterial infections may be more problematic. Lung infection post-transplant with pan-resistant organisms, especially B. cepacia, is worrisome. However, there is no higher incidence of pneumonia in CF lung recipients compared to those with other diagnoses [20,21].

The Toronto lung transplant program recently reported a 67% 1-year survival in 28 CF patients colonized with B. cepacia, compared to 92% in 25 patients without B. cepacia [9]. Thus, many programs in the US refuse to consider CF patients with B. cepacia as candidates for transplant. However, in the UK, colonization with B. cepacia was not associated with a poorer outcome [22]. Recently, seven species or genomovars of B. cepacia have been characterized. Patients infected with B. cepacia maintain the same strain for prolonged periods and some strains may be more biologically aggressive [23]. There may be strains associated with a poorer prognosis after transplant, a subject under investigation by the North American CF Foundation.

The presence or emergence of pan-resistant strains of Pseudomonas species is another area of controversy. An earlier analysis of our immediate pretransplant airway cultures retrieved from the operating room revealed that 27 of 66 CF patients harbored pan-resistant organisms at the time of transplant [24], and had identical survival compared to 39 CF patients with sensitive organisms. Development of resistance is likely an inevitable sequela of treating CF patients with antimicrobials for exacerbations. One of our post-transplant deaths due to necrotizing pneumonia was related to Pseudomonas species that was sensitive to antibiotics on in vitro testing. Accordingly, we do not feel that colonization with pan-resistant organisms per se is an absolute contraindication to transplant. B. cepacia has a particular proclivity to develop resistance once exposed to different antibiotics. Thus, in our view, it is irrational to accept CF patients for lung transplant who are colonized with B. cepacia, then deny them transplant when they demonstrate resistance. Neither the presence of Aspergillus nor atypical mycobacteria in the sputum of CF patients has had an adverse impact on outcome in our experience [20].

Colonization with B. cepacia is associated with a poorer outcome, both in our experience and in Toronto [9]. However, the 1-year actuarial survival for CF patients harboring B. cepacia is not dissimilar to the 68% 1-year survival of patients with idiopathic pulmonary fibrosis or 62% 1-year survival patients with primary pulmonary hypertension undergoing lung transplant in the US [1]. Not all deaths among patients colonized with B. cepacia, in our series were directly attributable to this organism. Beyond 6 months, the actuarial survival curves of B. cepacia-colonized CF patients and other CF patients are parallel (Fig. 2), implying that long-term survival does not appear to be adversely affected by presence of this organism, if patients survive the perioperative period.

Similarly, we feel that retransplant for BOS is still a reasonable option for selected patients who develop end stage lung disease due to BOS, provided there are no contraindications to transplant, i.e. that patients have been compliant and maintain good end organ function in all other body systems. Four of five retransplanted CF patients survived to discharge; the sole in-hospital death was due to an embolic stroke that occurred several days after a technically successful retransplant performed on cardiopulmonary bypass. Late deaths occurred in two retransplanted patients more than 3 years after retransplant due to development of severe acute pneumonia, which was presumably viral. Neither patient had evidence of BOS recurrence prior to their terminal event. Had these patients survived, the difference in survial between first time transplant and retransplant for BOS would likely be insignificant, although the small number of retransplants makes any statistical analysis unreliable.

BOS remains a significant cause of morbidity and mortality in lung transplant recipients. In an earlier analysis, we reported actuarial freedom from development of BOS is 90% at 1 year, but only 41% at 5 years, and 24% at 9 years, among surviving recipients of bilateral lung transplant for CF [18]. However, all three survivors of BLLTX are free from BOS after more than 5 years, consistent with the intriguing observation at University of Southern California (USC) that BOS is either delayed or less frequent in recipients of BLLTX [25].

BLLTX is an option for some patients with end stage lung disease. The recipient must be smaller than the two lower lobe donors, who must be in good health, with normal pulmonary function and have compatible blood types. The small stature of many CF patients makes some ideal candidates for consideration of BLLTX, but suitable donors frequently cannot be identified. The group at USC has reported better results with this procedure, but even in their hands, 1-year actuarial survival of 68% [13] is not equivalent to what we and others have achieved with bilateral cadaver lung transplantation. All nine of our BLLTX patients were in hospital with four on ventilators and one on bi-positive airway pressure (bi-PAP) at the time of BLLTX; arguably they were ‘sicker’ patients than the majority of our double lung transplant CF recipients who had ‘elective’ lung transplants. Ironically, the three long-term survivors of BLLTX were all receiving mechanical ventilation at the time of their transplant (Table 2).

The last decade has witnessed remarkable advances in understanding the pathophysiology of CF, including identification of a chloride channel abnormality, identification of a gene responsible for the chloride channel, and creation of a transgenic mouse with the genetic abnormality. Even before the genetic defect had been identified, it was demonstrated that the chloride channel epithelial abnormality present in CF was not manifested in the epithelium of heart–lung grafts transplanted into CF patients [26]. Improved understanding of the pathophysiology of the disease has led to improved care, which has translated into better survival. Currently CF life expectancy (median survival) is 29 years [1].

The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene fueled speculation that gene therapy would surely lead to a cure for CF. However, there are significant obstacles to permanent transfection of sufficient numbers of airway epithelial cells to effectively correct the Cl- ion transport mechanism. Gene therapy may be the future of CF treatment, but until these obstacles are overcome, lung transplant offers an opportunity to improve survival and quality of life in CF patients [27].

A better understanding of the pathophysiology of BOS is essential to improve long-term results. More selective immunosuppression may reduce the incidence of opportunistic infections and the risk of pneumonia. However, at our center, more CF patients have died on the waiting list than have died after lung transplant, underscoring the urgent need for more lung donors. Increasing the number of lung donors will make transplant more available, and may facilitate studies to improve our understanding of BOS.

Bilateral lung transplant has acceptable long-term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but lung transplantation is still warranted.


   Acknowledgments
 
The authors wish to acknowledge the valuable contributions to this manuscript of Dr I.P. Neuringer and Dr P. Rivera who could not be included as authors because of journal editorial policy. The authors also wish to gratefully acknowledge the excellent nursing care afforded to these patients by the dedicated nursing staff of CTICU, 4 Anderson South (CT Surgery units); 6 Bed Tower, RICU/MICU (Pulmonary Medicine units); the outstanding contribution of the Physical Therapy Department; and the contribution of many other members of the medical and support staff of UNC Hospitals who provided care to these patients.


   Footnotes
 
Presented at the joint 15th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 9th Annual Meeting of the European Society of Thoracic Surgeons, Portugal, September 16–19, 2001.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 References
 

  1. Patient Registry 1999 Annual Report. Bethesda, MD: Cystic Fibrosis Foundation. 2000.
  2. Hosenpud J., Bennett L., Berkeley M., Boucek M., Novick R. The Registry of the International Society for Heart and Lung Transplantation: eighteenth official report – 2001. J Heart Lung Transplant 2001;20:805-815.[Medline]
  3. Egan T.M., Detterbeck F.C., Mill M.R., Paradowski L.J., Lackner R.P., Ogden W.D., Yankaskas J.R., Westerman J.H., Thompson J.T., Weiner M., Cairns E.L., Wilcox B.R. Improved results of lung transplantation for patients with cystic fibrosis. J Thorac Cardiovasc Surg 1995;109:224-235.[Abstract/Free Full Text]
  4. Kerem E., Reisman J., Corey M., Canny G.J., Levison H. Prediction of mortality in patients with cystic fibrosis. N Engl J Med 1992;326:1187-1191.[Abstract]
  5. Ciriaco P., Egan T.M., Cairns E.L., Thompson J.T., Detterbeck F.C., Paradowski L.J. Analysis of cystic fibrosis referrals for lung transplantation. Chest 1995;107:1323-1327.[Abstract/Free Full Text]
  6. Massard G., Shennib H., Metras D., Camboulives J., Viard L., Mulder D.S., Tchervenkov C.I., Morin J.-F., Giudicelli R., Noirclerc M. Double-lung transplantation in mechanically ventilated patients with cystic fibrosis. Ann Thorac Surg 1993;55:1087-1092.[Abstract]
  7. Flume P.A., Egan T.M., Westerman J.H., Paradowski L.J., Yankaskas J.R., Detterbeck F.C., Mill M.R. Lung transplantation for mechanically ventilated patients. J Heart Lung Transplant 1994;13:15-21.[Medline]
  8. Snell G.I., de Hoyos A., Krajden M., Winton T., Maurer J.R. Pseudomonas cepacia in lung transplant recipients with cystic fibrosis. Chest 1993;103:466-471.[Abstract/Free Full Text]
  9. Chaparro C., Maurer J., Gutierrez C., Krajden M., Chan C., Winton T., Keshavjee S., Scvuzzo M., Tullis E., Hutcheon M., Kesten S. Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation. Am J Resp Crit Care Med 2001;163:43-48.[Abstract/Free Full Text]
  10. Meyers B., Sundaresan R., Guthrie T., Cooper J., Patterson G. Bilateral sequential lung transplantation without sternal division eliminates posttransplantation sternal complications. J Thorac Cardiovasc Surg 1999;117:358-364.[Abstract/Free Full Text]
  11. Egan T.M., Detterbeck F.C. Technique of lung transplantation. In: Kaiser L.R., Kron I.L., Spray T.L., eds. Mastery of cardiothoracic surgery. Boston, MA: Little Brown, 1998:167-177.
  12. Egan T.M., Thompson J.T., Detterbeck F.C., Lackner R.P., Mill M.R., Ogden W.D., Aris R.M., Paradowski L.J. Effect of size (mis)matching in clinical double-lung transplantation. Transplantation 1995;59:707-713.[Medline]
  13. Starnes V.A., Barr M.L., Cohen R.G., Hagen J.A., Wells W.J., Horn M.V., Schenkel F.A. Living-donor lobar lung transplantation experience: intermediate results. J Thorac Cardiovasc Surg 1996;112:1284-1291.[Abstract/Free Full Text]
  14. Frist W.H., Fox M.D., Campbell P.W., Fiel S.B., Loyd J.E., Merrill W.H. Cystic fibrosis treated with heart–lung transplantation: North American results. Transplant Proc 1991;23:1205-1206.[Medline]
  15. Yacoub M.H., Banner N.R., Khaghani A., Fitzgerald M., Madden B., Tsang V., Radley-Smith R., Hodson M. Heart–lung transplantation for cystic fibrosis and subsequent domino heart transplantation. J Heart Transplant 1990;9:459-467.[Medline]
  16. de Leval M.R., Smyth R., Whitehead B., Scott J.P., Elliott M.J., Sharples L., Caine N., Helms P., Martin I.R., Higenbottam T., Wallwork J. Heart and lung transplantation for terminal cystic fibrosis: a 4-1/2-year experience. J Thorac Cardiovasc Surg 1991;101:633-642.[Abstract]
  17. Ramirez J.C., Patterson G.A., Winton T.L., de Hoyos A.L., Miller J.D., Maurer J.R., Toronto Lung Transplant Group. Bilateral lung transplantation for cystic fibrosis. J Thorac Cardiovasc Surg 1992;103:287-294.[Abstract]
  18. Egan T.M., Detterbeck F.C., Mill M.R., Gott K.K., Rea J.B., McSweeney J., Aris R.M., Paradowski L.J. Lung transplantation for cystic fibrosis: effective and durable therapy in a high-risk group. Ann Thorac Surg 1998;66:337-346.[Abstract/Free Full Text]
  19. Mendeloff E.N., Huddleston C.B., Mallory G.B., Trulock E.P., Cohen A.H., Sweet S.C., Lynch J., Sundaresan S., Cooper J.D., Patterson G.A. Pediatric and adult lung transplantation for cystic fibrosis. J Thorac Cardiovasc Surg 1998;115:404-414.[Abstract/Free Full Text]
  20. Flume P.A., Egan T.M., Paradowski L.J., Detterbeck F.C., Thompson J.T., Yankaskas J.R. Infectious complications of lung transplantation: impact of cystic fibrosis. Am J Respir Crit Care Med 1994;149:1601-1607.[Abstract]
  21. Maurer J.R., Tullis D.E., Grossman R.F., Vellend H., Winton T.L., Patterson G.A. Infectious complications following isolated lung transplantation. Chest 1992;101:1056-1059.[Abstract/Free Full Text]
  22. Egan J., McNeil K., Bookless B., Gould K., Corris P., Higgenbottam T., Webb A., Woodcock A. Post-transplantation survival of cystic fibrosis patients infected with Pseudomonas cepacia. Lancet 1994;344:552-553.[Medline]
  23. Steinbach S., Sun L., Jiang R.-Z., Flume P., Gilligan P., Egan T.M., Goldstein R. Transmissibility of Pseudomonas cepacia infection in clinic patients and lung-transplant recipients with cystic fibrosis. N Engl J Med 1994;331:981-987.[Abstract/Free Full Text]
  24. Aris R.M., Gilligan P.H., Neuringer I.P., Gott K.K., Rea J., Yankaskas J.R. The effects of panresistant bacteria in cystic fibrosis patients on lung transplant outcome. Am J Respir Crit Care Med 1997;155:1699-1704.[Abstract]
  25. Starnes V., Woo M., MacLaughlin E., Horn M., Wong P., Rowland J., Durst C., Wells W., Barr M. Comparison of outcomes between living donor and cadaveric lung transplantation in children. Ann Thorac Surg 1999;68:2279-2283.[Abstract/Free Full Text]
  26. Wood A., Higenbottam T., Jackson M., Scott J., Stewart S., Wallwork J. Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation. Am Rev Respir Dis 1989;140:1645-1649.[Medline]
  27. Caine N., Sharples L.D., Dennis C., Higgenbottam T.W., Wallwork J. Measurement of health-related quality of life before and after heart–lung transplantation. J Heart Lung Transplant 1996;15:1047-1058.[Medline]



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