Lung transplantation for cystic fibrosis

PURPOSE OF REVIEW: To examine recent publications on lung transplantation for cystic fibrosis for changes in surgical techniques, selection criteria of patients, and impact on quality of life. RECENT FINDINGS: Recent evidence focuses on cystic fibrosis patient subsets enabling better decisions about listing for lung transplantation as a therapeutic option. There is information about Burkholderia cepacia infection, ventilator dependence, young age, and arthropathy. In the US, the United Network for Organ Sharing has addressed perceived inequities in organ distribution by allocating organs by illness severity rather than time on the waiting list. A Lung Allocation Score ranks severity for patients 12 years of age and older for transplantation based on variables including lung function, oxygen and ventilatory needs, diabetes, weight and physical performance. Some recently studied important variables that influence survival in cystic fibrosis and after lung transplantation, including airway infections, pancreatic exocrine function and acute exacerbations, are not included in the Lung Allocation Score. Few publications have examined quality of life after transplantation, and a definitive work has yet to appear. SUMMARY: New information has refined decision-making about lung transplantation for patients with cystic fibrosis. We examine recent findings and make recommendations for patients, families and medical providers.     

Lung transplantation in cystic fibrosis.

Lung transplantation has emerged in the last decade as a valid therapeutic endeavor for patients with end-stage lung disease. Although the presence of highly resistant organisms in the airway and sinuses of patients with cystic fibrosis (CF) increases the perioperative risk of infection following lung transplantation, transplant procedures can be undertaken in properly selected CF patients with acceptable morbidity and mortality at experienced centers. The introduction of a modification in the technique of double-lung transplantation has resulted in improved operative survival of CF patients undergoing lung transplantation. Whereas problems with posttransplant obliterative bronchiolitis, infection, and lymphoproliferative disorders contribute to morbidity, it is clear that lung transplantation can offer CF patients with end-stage lung disease improvement in both the quality and quantity of life. The most serious impediment to more widespread application of this therapy in CF is the inadequate number of donor organs.     

Lung transplantation in patients with cystic fibrosis

Worldwide more than 600 heart-lung or lung transplantations have been performed in patients with cystic fibrosis and end-stage respiratory disease. At the University Hospital in Groningen 10 patients with cystic fibrosis underwent bilateral sequential lung transplantation until April 1994. The 1-year survival was 76%, which is similar to that of lung transplant recipients with other diseases. Postoperative problems were mainly related to acute rejection, chronic graft dysfunction and infection. The main problem for further extension of the lung transplantation program is the persistent shortage of usable donor-organs for cystic fibrosis patients, especially of small-sized donors.     

Special considerations for patients with cystic fibrosis undergoing lung transplantation

This article reviews lung transplantation in patients with cystic fibrosis (CF). Lung transplantation is commonly utilized for patients with end-stage CF. There are several characteristics of CF that present unique challenges before and after lung transplantation. There is new information available that can be utilized to predict outcomes in patients with end-stage CF, and therefore can help in decisions of referral and listing for lung transplantation. The new lung allocation score, which allocates organs to patients who are on the lung transplant waiting list in the United States, presents new challenges and opportunities for patients with end-stage CF. In addition, the effect of the presence of microbiological flora prior to lung transplantation has been better linked to outcomes after lung transplantation. It is now known that, other than those patients harboring Burkholderia cepacia in their lungs before transplantation, most CF patients can undergo transplantation successfully. Nutrition remains an important issue among CF patients, and diabetes is a common problem after lung transplantation. In contrast, liver disease does not usually present major problems but, if it is severe, can necessitate liver and lung transplantation. Mechanical ventilation prior to transplantation might not be an absolute contraindication for CF patients. CF lung transplant recipients have good outcomes after lung transplantation compared with those of other lung transplant recipients. Quality of life is dramatically improved. However, they are still prone to common complications that all lung transplant recipients are prone to, including primary graft dysfunction, acute and chronic rejection, a variety of infections and malignancies, and renal failure.     

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience

Liver disease develops in one‐third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.     

Lung function decline in cystic fibrosis patients and timing for lung transplantation referral

STUDY OBJECTIVES: To determine risk factors associated with an accelerated decline in lung function in cystic fibrosis (CF), and whether longitudinal changes in FEV(1) would be a better predictor of the need for referral for lung transplantation than any single value for FEV(1.) DESIGN: The rate of decline in pulmonary function was determined by standard linear regression from each patient's calendar year's best percentage of predicted FEV(1) (%FEV(1)) over at least 4 years, and patients were classified into three cohorts based on their rate of decline. Differences between groups in age, weight-for-age z score, gender, genotype, pancreatic status, diabetes, and the presence of various lung microbial isolates were analyzed. A subset of 30 patients referred for lung transplantation were further analyzed, and a prediction model for lung transplantation referral was created using the patient's rate of decline in lung function, the mean waiting time for donor organs, and the average level of lung function of patients prior to lung transplantation. PATIENTS: One hundred fifty-three patients with CF followed up at the Washington University Adult Cystic Fibrosis Center. RESULTS: Younger age, malnutrition, and concurrent infection with both Pseudomonas aeruginosa and Staphylococcus aureus were significant (p < 0.05) risk factors for rapidly declining lung function. Among patients with rapidly declining lung function, referral for lung transplantation would have occurred 8.4 months earlier than actual referral age (p < 0.05) if the prediction model had been used, possibly resulting in additional patient salvage in several cases. CONCLUSIONS: Rate of decline in lung function should be routinely evaluated in patients with CF, and a prediction model utilizing the rate of decline in %FEV(1), and the median regional waiting period for donor lungs for patients with CF may assist in the timing of referral for lung transplantation and more rapidly declining lung function.     

Lung transplantation: disease-specific considerations for referral

The timing of the referral and listing of patients for lung transplantation remains a difficult decision. Life expectancy and quality of life with and without transplantation are the pivotal issues that need to be considered by physicians and presented to prospective transplant candidates. The recognition of recent advances in the understanding of the various primary diseases, other potential therapies, and the latest posttransplant statistics are essential for a balanced discussion or decision about lung transplantation. This article provides a review of these and other pertinent issues for patients with various forms of advanced lung disease.     

Successful heart-lung transplantation for cystic fibrosis

Sixteen months after heart-lung transplantation, the FEV1 of a young woman, who had been in the terminal stages of cystic fibrosis, has risen from 16 percent (0.6 L) to 77 percent of her predicted value. Concomitant with the changes in pulmonary function, her ventilatory response to re-breathing carbon dioxide has improved, and so has her exercise tolerance. She has returned to work.     

Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes

BACKGROUND: Men with cystic fibrosis (CF) have bilateral absence of the vas deferens causing an obstructive azoospermia that is not amenable to surgical correction. Advances in the field of reproductive medicine allow for the procurement of viable sperm and facilitate fertilization and pregnancy in couples where the man has CF. OBJECTIVES: To describe patient anatomy and semen characteristics and to determine the pregnancy rates of couples in whom the male partner has CF and who have undergone microsurgical epididymal sperm aspiration coupled with in vitro technology, specifically intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective analysis. SETTING: Clinical department of urology and two reproductive medicine units. PATIENTS: Thirteen married men with CF who were referred for infertility. INTERVENTIONS: History, physical examination, semen analysis, transrectal and renal ultrasonography, CF mutation analysis, and microsurgical sperm aspiration coupled with ICSI. RESULTS: All 13 men had low-volume azoospermia, absent vasa, and aplasia/hypoplasia of the seminal vesicles. CF mutation analysis was carried out in 11 of 13 men, and 9 of 11 were DeltaF508 homozygous. Eight men underwent microsurgical sperm aspiration, and their partners underwent one or more cycles of ICSI. Five couples (62.5%) achieved a pregnancy, with four couples delivering (three sets of twins and one singleton). CONCLUSIONS: CF in men is accompanied by bilateral vasal aplasia. The resultant obstructive azoospermia can be treated quite successfully with a combination of sperm aspiration and ICSI. It is important for physicians involved in the care of men with CF to convey the message that prospects for fatherhood are excellent with current technology.     

Transplantation for cystic fibrosis: outcome following early liver transplantation

BACKGROUND AND AIM: Life expectancy in patients with cystic fibrosis (CF) has recently improved due to numerous factors, including a multidisciplinary approach to their management. Prolonged survival may have led to an increasing impact of liver disease on the prognosis of CF patients. The aim of this study was to assess the role of liver transplantation in patients with CF. METHODS: The factors influencing outcome in 24 patients (15 adults and nine children) with CF who have received single liver transplantation, triple heart-lung-liver transplantation (tx) or died while being assessed for triple grafting, were analyzed. RESULTS: Median age at tx in single liver recipients (13 years) was lower than in triple graft recipients (21 years) and those who died (23 years). All patients who received single liver tx made an excellent recovery, including significant improvement of their respiratory function (mean forced vital capacity (FVC) increased from 61% before transplantation to 82% of expected, 6-9 months after tx). Four out of five patients who received triple tx died (0-2 months) after operation. On the basis of our retrospective review, we propose modifications to an existing scoring system for liver tx assessment in CF by scoring additional points for elevated white blood count, bilirubin, and impaired pulmonary function. These changes will need to be evaluated prospectively to confirm their predictive value. CONCLUSIONS: Liver transplantation is effective therapy in young patients with cystic fibrosis, portal hypertension and hepatic dysfunction, and is indicated before a critical stage of deteriorating lung function is reached. In patients with both end-stage liver and lung disease, triple tx has a poor prognosis. Pre-emptive liver tx in younger patients with CF not only has a better outcome but improves lung function.     

Liver transplantation for cirrhosis in cystic fibrosis.

BACKGROUND: Liver disease is the third most common cause of death in children with cystic fibrosis (CF). Liver transplantation is an effective treatment in children with hepatic failure. AIMS: The objective of the present study was to review the indications and postoperative course of hepatic transplantation in a cystic fibrosis population. PATIENTS: Five children with CF, at a mean age of 16.5 years, underwent liver transplantation. RESULTS: All patients showed cirrhosis, portal hypertension and hepatic failure. The main postoperative complication was ascites refractory to treatment in two patients. No significant deterioration of the pulmonary function was noted. Two patients died, one of Hodgkin lymphoma and the other of progressive pulmonary failure. CONCLUSION: Liver transplantation was indicated in children with CF when hepatic failure and/or severe portal hypertension was present with well-preserved pulmonary function.