The most frequent indication for lung transplantation in Spanish adults is emphysema/COPD, followed by idiopathic pulmonary fibrosis. These two diseases represent more than 60% of total LT indications (Table 2).

Fig. 3a shows the evolution over time of the main indications for lung transplantation. A progressive increase is observed in the indication for transplant due to emphysema/COPD that is relatively stable and greater than other indications.

Fig. 3.

Evolution of the most frequent indications for adult lung transplantation (Spanish Lung Transplant Registry, 2006–2010).

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The procedure type varies depending on the indication for transplantation (Fig. 3b). Bilateral transplant is the most frequent indication in cases of cystic fibrosis, which represents 100% of the cases in 2009 and 2010. Single-lung transplants predominate in patients with pulmonary fibrosis, although bilateral transplants seem to be increasing in frequency in the last 2 years. In emphysema/COPD, the distribution is almost 50% for each type of procedure.

Approximately one-third of patients who survived the first year port-transplantation have experienced at least one documented episode of acute rejection in this period, as shown in Fig. 4. This figure also presents this percentage broken down according to recipient sex and age groups.

Fig. 4.

Percentage of adult patients who were treated for acute rejection between 15 days and one year post-transplantation (Spanish Lung Transplant Registry, 2006–2010); analysis limited to one-year post-transplantation survivors.

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We have data available regarding induction immunosuppressive therapy for 541 adult lung transplant recipients (57% of the total), which may affect the representative nature of the sample in this section. Out of the 541, 32% received induction therapy, mainly anti-CD25 monoclonal antibody (basiliximab). The survival analysis shows a significant improvement in the patients who received induction therapy compared with those who did not receive this treatment (Fig. 5a); the difference is established between both groups between days 15 and 45 post-transplantation, after which it remained stable.

Fig. 5.

Survival curve associated with immunosuppressive induction (a); maintenance immunosuppression used in adult lung transplant recipients one week (b) and one year (c) post-transplantation (% patients) (regardless of the use of steroids in the combination) (Spanish Lung Transplant Registry, 2006–2010).

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Most patients received triple immunosuppressive maintenance therapy, including steroids and a calcineurin inhibitor+an antimetabolic agent (Fig. 5b and c). Tacrolimus, together with mycophenolate mofetil or mycophenolic acid, has been predominantly used in recent years.

Fig. 6 shows the survival of adult lung transplant patients in Spain between 2006 and 2010. There are no significant differences in the survival observed between single-lung or bilateral transplantations. As in other registries, a tendency was observed toward presenting greater survival in patients with bilateral transplants (P=.190). However, other important factors should be considered, such as age (bilateral recipients are younger) that impact survival and may be a cause for bias in the results.

Fig. 6.

Survival curves (Kaplan–Meier, log rank), both global and by procedure type in adult lung transplant recipients (Spanish Lung Transplant Registry, 2006–2010).

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Unadjusted survival rates for 3 months, one year and 3 years were 79.9%, 71.7%, and 60.1%, respectively. In the patients who survive until the third month, one-year survival is 89.7% and 3-year survival is 75.2%. Better survival is observed when the recipients are under the age of 50 at the time of the transplantation (Fig. 7b).

Fig. 7.

Survival curves (Kaplan–Meier, log rank) of adult lung transplant recipients according to donor age (a), recipient age (b) and indication for transplantation (c) and (d) (Spanish Lung Transplant Registry, 2006–2010).

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Survival is different depending on the disease indicating the transplantation (Fig. 7c). Those receiving transplants due to idiopathic pulmonary hypertension have the poorest survival: 46% at three months. The limited number of cases with this indication for transplantation means that these data should be analyzed with caution, although in the literature greater perioperative mortality in this pathology.2 At the opposite extreme, with the best post-transplant survival rates, there are transplanted cystic fibrosis patients. When we analyze the conditioned survival starting at the third month post-transplantation (Fig. 7d), the differences are not as notable, although cystic fibrosis is still the indication with the greatest survival. This could be related with the fact that these patients are generally younger, although the difference also remains after adjusting for recipient age.

No statistically significant differences are observed in survival according to donor age (Fig. 7a), although the group of donors aged 50–59 present the poorest results. The better survival observed with donors aged 60 or older compared with the preceding age group may be due to the fact that these older donors are only selected if they meet all the criteria for suitability except for age, and thus may possibly present better overall characteristics despite their advanced age. When the donor cut-off age is set at 55, the limit that is usually used for “ideal” donors, there seems to be an observed tendency toward shorter survival in patients transplanted from older donors (P=.138).

As for CMV serostatus pairing between donor and recipient, the serologic state of the donor seems to have a greater influence (P=.099) than pairing itself (P=.244) and better results are seen when the donor is negative, although the difference does not reach statistical significance. It is important to take into account that this datum was not available for all recipients (n=514), and it is therefore recommended to interpret these results with caution as this limitation may introduce bias.

The causes of death are presented in Table 3. Infections were the most frequent cause of mortality in the 3 periods analyzed.

A univariate study was done of the risk factors for mortality one year post-transplant (Table 4). As explained in the methodology, to ensure a one-year follow-up we only included in the analysis those transplants done between 2006 and 2009. The analysis includes several variables from the donor, recipient and the transplantation procedure itself. The influence of other factors was also analyzed, like the use or not of induction immunosuppressive therapies and the volume of annual transplantations done by the transplant centers.

No association was found between the majority of the donor characteristics and one-year mortality in the adult lung transplant recipients. Only age seems to present a tendency to influence said mortality (Fig. 8a).

Fig. 8.

Risk for one-year mortality (log rank) of the adult lung transplant recipient according to donor age (a), recipient age (b), BMI (c) and annual volume of lung transplantations per center (d) (Spanish Lung Transplant Registry, 2006–2009).

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A poorer result is observed in the recipients aged between 50 and 59. In fact, there is a significant relationship (P=.006) between the age of the recipient and mortality one year after transplantation (Fig. 8b). Fig. 8c shows the directly proportional relationship obtained between recipient BMI and mortality in this time period.

All the indications for transplantation presented greater one-year mortality than cystic fibrosis. Re-transplantations due to acute problems in the immediate post-transplantation period, especially due to primary graft failure (generally related with procedures done in emergency situations), present a survival that is approximately 4 times lower than those who were not re-transplanted within the first year. It is important to highlight that re-transplantation due to chronic graft deterioration (bronchiolitis obliterans syndrome) does not present poorer one-year survival.

The number of transplantations done annually at the transplantation hospitals is also related with one-year survival (P=.001), and the results are generally better as the annual transplantation activity increases (Fig. 8d). A study done with data from the United Network for Organ Sharing (UNOS) registry found this same association.4

Twelve cases of malignant neoplasms have been reported in the patients who survived one year after transplantation, which represents an incidence of 3.2%. The origins of the neoplasms were: 6 cases of lymphoproliferative disease (including one Kaposi's sarcoma), 5 organ carcinomas and a cutaneous basal-cell carcinoma.

The most frequent cause of lung transplantation in the patients under the age of 16 was cystic fibrosis, and the procedure used in more than 95% of the cases was bilateral transplantation (Table 5).

The survival curve of the pediatric transplantations is shown in Fig. 9. The unadjusted survival rates at 3 months, 1 year and 3 years are 90.3%, 80%, and 66.9%, with an No. at risk of 27, 21, and 4, respectively.

Fig. 9.

Survival curve (Kaplan–Meier) of the pediatric lung recipients (n=31) (Spanish Lung Transplant Registry, 2006–2010).

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The limited number of pediatric transplantations does not allow for more detailed analyses.

There were 11 deaths among the 31 pediatric transplant recipients between the years of 2006 and 2010. Details about the causes of death are given in Table 6.

The limited number of pediatric transplantations does not allow for the study of mortality risk factors.

Three cases were reported of malignant disease between the 14 patients with more than one year of follow-up, which was determined to be post-transplantation lymphoproliferative disease in each case.