True Survival Benefit of Lung Transplantation for Cystic Fibrosis Patients: The Zurich Experience

doi:10.1016/j.healun.2008.12.025

The Journal of Heart and Lung Transplantation

Volume 28, Issue 4, April 2009, Pages 334-339

Presented in abstract form at the 2008 European Cystic Fibrosis Society Meeting, Prague, Czech Republic.

https://doi.org/10.1016/j.healun.2008.12.025 Get rights and content

Background

Lung transplantation is the ultimate therapy for end-stage cystic fibrosis (CF) lung disease; however, the debate continues as to whether lung transplantation improves survival. We report post-transplant outcome in CF at our institution by comparing 5-year post-transplant survival with a calculated 5-year survival without lung transplantation, using a predictive 5-year survivorship model, and describe pre-transplant parameters influencing transplant outcome.

Methods

CF patients undergoing lung transplantation at our center were included (1992 to 2007). Survival rates were calculated and compared, and univariate and multivariate Cox regression analyses were used for statistical assessment.

Results

Eighty transplants were performed in CF patients, 11 (13.8%) of whom were children. Mean age at transplant was 26.2 years (95% confidence interval: 24.4 to 28.0). The Liou raw score at transplant was −20 (95% confidence interval: −16 to −24), resulting in an estimated 5-year survival without transplantation of 33 ± 14%, compared with a 5-year post-transplant survival of 68.2 ± 5.6%. Further improvement was noted in the recent transplant era (since 2000), with a 5-year survival of 72.7 ± 7.3%. Univariate analysis revealed that later year of transplant and diagnosis of diabetes influenced survival positively. Pediatric age had no negative impact. In the multivariate analysis, only diabetes influenced survival, in a positive manner.

Conclusion

Lung transplantation performed at centers having experience with the procedure can offer a true survival benefit to patients with end-stage CF lung disease.

Section snippets

Study Population

In this study we included all pediatric and adult CF patients undergoing primary lung transplantation at the University Hospital Zurich, Switzerland, between November 1992 and November 2007. Transplant recipients were followed-up until August 2008. Patients' demographic data were collected. Pre-transplant clinical data included forced expiratory volume in 1 second (FEV₁), body mass index (BMI), diagnosis of CF-related diabetes mellitus (CFDM) and bone mineral density at the hip/femoral neck

Study Population

Two hundred thirty lung transplant operations have been performed in our program since its establishment in 1992 up to November 2007. Of this cohort, 80 (34.5%) transplant recipients had CF, all of whom were included in this study (13.8% were <18 years of age). All except 1 patient underwent double-lung transplantation. One patient with additional congenital heart disease had a heart–lung transplant operation performed. Two CF patients were chronically infected with Burkholderia cepacia

Discussion

This observational study demonstrates a true survival benefit for CF patients with end-stage lung disease undergoing lung transplantation at our center. Estimated 5-year survival without transplantation in our cohort was 33% compared with a 5-year survival after transplantation of 67%. Moreover, the 1-year post-transplant survival in the recent era (since 2000) improved to >90% in CF transplant recipients, and for 3-year survival was >80%. Furthermore, pediatric age had no negative impact on

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Cited by (63)

Management of Sinusitis in the Cystic Fibrosis Patient
2020, Immunology and Allergy Clinics of North America
An aging population of patients with cystic fibrosis undergoes lung transplantation: An analysis of the ISHLT Thoracic Transplant Registry
2019, Journal of Heart and Lung Transplantation
Citation Excerpt :
The indication of CF has comprised about 15% of adult primary lung transplants and just over half of the pediatric primary lung transplants. Studies have suggested that lung transplant confers a survival benefit for adults with CF.5,6 However, studies overall have not demonstrated clearly a survival benefit for children with CF undergoing lung transplantation,15–18 though a few single-center studies have suggested otherwise.6,19 Pediatric patients after primary lung transplant had a median 5-year survival of >50% in the latest transplant era, similar to adult recipients.11,12
Since lung transplantation became a viable option for cystic fibrosis (CF) lung disease, adult transplant recipients with CF have superior survival than all the other major diagnostic indications. However, among adults, recipients with CF have a younger age at transplant than other transplant recipients. Over time, the frequency and proportion of lung transplants for CF has increased for adults compared with children. Using a large international transplant registry, we investigated time trends in numbers of transplants, age at transplant, and post-transplant survival and cause of death for recipients with CF.
We conducted a retrospective cohort study of primary lung-alone deceased-donor transplants with a primary diagnostic indication of CF reported to the International Society for Heart and Lung Transplantation Thoracic Transplant Registry from January 2005 through December 2014. We assessed outcomes through December 31, 2015. The study defined the pediatric group as age <18 years at transplant and the adult as ≥18 years at transplant. We assessed time trends (Era I 2005–2009, Era II 2010–2014) in age and compared post-transplant outcomes of age sub-groups with Kruskal–Wallis or chi-square tests. Kaplan–Meier survival analysis estimated the incidence of survival, censoring for loss to follow-up, end of study, and retransplant. In addition, we compared outcomes in age groups and transplant eras with the log-rank test.
Of the 5,613 transplanted recipients with CF, the pediatric group comprised 10.9% and the adult group comprised 89.1%. Of the adults, 73.3% were aged 18 to 39 years and 15.9% were ≥40 years old. During Era I, 2,508 of transplant recipients had CF, whereas 3,105 recipients had CF in Era II (p < 0.001). Comparing Era I with Era II, recipient mean age increased from 28.4 years to 29.5 years (p < 0.001) and the proportion of pediatric CF recipients dropped from 12.4% to 9.6% (p < 0.001), whereas the proportion with age ≥40 years increased from 14.2% to 17.2% (p < 0.001). Mean donor age was significantly lower in children than in recipients aged 18 to 39 years and ≥40 years (17.0 vs 37.0 vs 41.0 years, p < 0.001). Pediatric CF transplant recipients had lower survival in the first 3 years post-transplant than adults (p < 0.0001). Chronic graft failure caused most pediatric deaths, whereas infection was the leading cause of death in adult recipients.
As survival of patients with CF has improved in recent decades, the mean age of lung transplant recipients with CF has increased. Currently, an increasing number of adults undergoes lung transplant for this indication. Adult CF transplant recipients continue to have better survival than pediatric recipients, and among adults, older adults have had better survival than younger adults.
Question 13: Can we predict the need for lung transplantation in children with cystic fibrosis?
2019, Paediatric Respiratory Reviews
Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation
2018, Archivos de Bronconeumologia
La enfermedad pulmonar es la principal causa de mortalidad en el 80% de los pacientes con fibrosis quística (FQ). La influencia de la circulación extracorpórea (CEC) no está completamente establecida. Los objetivos son evaluar los resultados del trasplante pulmonar por FQ en un solo centro y la influencia de la CEC sobre la supervivencia de estos pacientes.
Estudio observacional retrospectivo de todos los pacientes afectados de FQ trasplantados en un solo centro entre 1992 y 2011. En este período se han realizado 64 trasplantes pulmonares por FQ.
La supervivencia de los pacientes trasplantados a los 5 y 10 años fue del 56,7 y el 41,3%, respectivamente. El requerimiento de oxígeno suplementario previo al trasplante no parece afectar a la supervivencia (p = 0,44), al igual que los pacientes que se trasplantaron con ventilación mecánica no invasiva (p = 0,63). La supervivencia a los 5 y 10 años para los pacientes que no se trasplantan con CEC es del 75,69 y el 49,06%, respectivamente, mientras que los que se trasplantan bajo CEC tienen un supervivencia a los 5 y 10 años del 34,14 y el 29,87%, respectivamente (p = 0,001). La PaCO₂ es un factor de riesgo independiente para la necesidad de CEC.
Los pacientes con FQ trasplantados pulmonares en nuestro centro tiene una supervivencia similar a la descrita por los registros internacionales. Los pacientes trasplantados bajo CEC tienen una menor supervivencia. La PaCO2 es factor de riesgo de necesidad de CEC durante el trasplante pulmonar.
Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival.
We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed.
Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO₂ is an independent risk factor for the need for ECC.
The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO₂ is a risk factor for the need for ECC during lung transplantation.
The changing epidemiology and demography of cystic fibrosis
2017, Presse Medicale
Citation Excerpt :
Several factors including sex, malnutrition, and CFRD have been shown to have a negative impact on health outcomes in the general CF population [21,27,28,57,58]; however, their effects on the post-transplant population are less clear. For example, depending on the study, investigators have found that individuals with CFRD have better survival post-transplant [59,60] an increased the risk of death following lung transplant [55], or no association to post-transplant survival [54]. Furthermore, female sex or the presence of malnutrition has been shown to have a negative impact on overall CF survival but it is uncertain if these are important predictors in the post-transplant patient population.
Once considered a pediatric disease with a poor prognosis, individuals born with cystic fibrosis (CF) today can expect to live well into adulthood. The implementation of multidisciplinary care, novel treatments and newborn screening has resulted in the rapid evolution in the demographics of the CF population. The purpose of this review is to highlight the evolving epidemiology and demographics of the CF population internationally.
Transplantation
2016, Pediatric Clinics of North America
Citation Excerpt :
All these questions await further studies. Bilateral LTx and OLT offer survival benefits to patients with end-stage CF lung or liver disease if selected appropriately and timed well.88 It is not an easy path.

View all citing articles on Scopus

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Clinical lung and heart/lung transplantationTrue Survival Benefit of Lung Transplantation for Cystic Fibrosis Patients: The Zurich Experience

Background

Methods

Results

Conclusion

Section snippets

Study Population

Study Population

Discussion

Update on cystic fibrosis: selected aspects related to lung transplantation

Swiss Med Wkly

Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult lung and heart–lung transplantation report—2008

J Heart Lung Transplant

Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria

J Heart Lung Transplant

Survival following lung transplantation of cystic fibrosis patients colonized with Burkholderia cepacia

Am J Respir Crit Care Med

Outcomes of lung transplantation for cystic fibrosis in a large UK cohort

Thorax

Lung transplantation and life extension in children with cystic fibrosis

Lancet

Quality of life after lung transplantation: a cross-sectional study

J Heart Lung Transplant

Lung transplantation and survival in children with cystic fibrosis

N Engl J Med

Lung transplantation and survival in children with cystic fibrosis: solid statistics—flawed interpretation

Pediatr Transplant

Lung transplantation and survival in children with cystic fibrosis

N Engl J Med

Lung transplantation and survival in children with cystic fibrosis

N Engl J Med

Predictive 5-year survivorship model of cystic fibrosis

Am J Epidemiol

Survival effect of lung transplantation among patients with cystic fibrosis

JAMA

International guidelines for the selection of lung transplant candidates: 2006 update—a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation

J Heart Lung Transplant

Clinical lung and heart/lung transplantation
True Survival Benefit of Lung Transplantation for Cystic Fibrosis Patients: The Zurich Experience