In recent years, lung transplantation has become established as a therapeutic option for children with severe lung disease in whom other therapeutic options have failed, resulting in good quality of life and prolonged survival, similar to that of transplants performed in adults.1

Pediatric transplantation has numerous unique features in relation to transplantation in adults2: specific characteristics of children at different stages of development (from infants to adolescents), different indications for different age groups, the effects of immunosuppressant treatments, special susceptibility to infections related to an immature immune system, and particular problems in the availability of suitable donors.

Although pediatric transplant results have improved considerably in the last two decades3 due to advances in the transplant technique, organ preservation, peri-operative management, immunosuppression, and the prophylaxis and treatment of infectious complications, as in adults, chronic graft dysfunction limits long-term survival.

The first transplant in an adult in Spain was carried out in 1990. Six transplants were performed that year, with the number of annual transplants increasing gradually to 238 in 2012, to a total of 2940 [Spanish National Transplant Organization (ONT) data].4,5 The ONT considers pediatric transplants as those performed in children under the age of 16. The first pediatric lung transplant was carried out in 1996.6 Since then, 114 pediatric transplants have been performed in Spain, accounting for 3.9% of the total.4 Unlike adult transplants, the annual number of transplants has remained relatively steady, with a median of 6 per year during this period (Fig. 1). In the Spanish Lung Transplant Registry, 74% of children were aged between 11 and 15 years old.5 These data are comparable with those recorded in the registry of the International Society for Heart & Lung Transplantation (ISHLT),1,7 in which pediatric transplantation is considered to be a transplant carried out in children aged under 18. According to ISHLT data, 49,673 lung and heart-lung transplants were performed between 1987 and June 2012, 2542 (5.12%) of which were pediatric. The highest percentage of transplants took place in the adolescent group (12–17 years), representing 84% of pediatric transplants in Europe and 68% in North America.1 In this registry, a very modest increase in the number of pediatric transplants was observed from the 73 carried out in 2000 to 107 in 2011, peaking at 125 transplants in 2010.1

Figure 1.

Evolution of the number of pediatric and adult lung transplants performed in Spain during the years 1990–2012 (National Transplant Organization data 4).

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The low frequency of transplants in children and absence of an increase similar to that in adult patients is related to 3 factors8:

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  The low prevalence of severe lung disease in children.

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  Advances in the medical care of patients with cystic fibrosis9 (the primary indication in pediatric patients) have considerably improved its course and delayed the age at which lung transplantation may be required.

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  The limited availability of young donors.

Only a small number of hospitals worldwide carry out pediatric lung transplantation (around 40), and most (88.3%) perform between 1 and 4 transplants per year only, with just 3–4 centers performing between 5 and 9 transplants and 2 centers between 10 and 19 transplants.1 As in Spain, two types of centers can be distinguished among these: centers specifically dedicated to pediatric transplantation, in which transplants are performed in children of all ages (or in some centers in children above preschool age), and adult lung transplant centers in which adolescents or children over 8–10 years of age are also treated.10

As in adults, the general indication for lung transplantation is progressive respiratory failure with a short life expectancy, generally less than 1–2 years, and very poor quality of life.2,11 It requires that all other therapeutic measures have been exhausted, there is no other serious illness, the ability to comply with a complex therapeutic regimen has been assessed, there is a suitable social environment and the family and/or the child assumes the risks of the transplant.

Table 1 specifies the main diseases in which lung transplantation may be indicated in children. Cystic fibrosis is the most common indication; the other major groups of indications are pulmonary vascular diseases (mainly pulmonary hypertension) and diffuse parenchymal lung diseases.12–16

In the Spanish Lung Transplant Registry (2006–2010),5 cystic fibrosis accounted for 67.75% of transplants in children aged under 16, post-infectious bronchiolitis obliterans for 12.95%, pulmonary arterial hypertension for 3.2% and interstitial lung diseases, 16.1%. Table 2 shows the number of pediatric transplants carried out in our hospital during the period 1996–2012, with the relative frequency of the different indications.

The proportion of the different indications in relation to age groups has changed in recent years. In the ISHLT registry, cystic fibrosis accounts for 53.8% of transplants in children aged between 6 and 11 years, and 71.5% in those aged between 12 and 17 years.1 It should be taken into consideration, however, that the ISHLT registry includes data from 1990, and that transplant in children under 11 and adolescents with cystic fibrosis is becoming increasingly less common. According to data from the Catalonian lung transplant registry (Spain), cystic fibrosis represents less than 10% of transplants performed in children under 11 years, but 85% of those carried out in adolescents aged between 12 and 17 years.17

The decision to place a child on the waiting list for a lung transplant is not easy, as it is very difficult to predict survival. It is very important to make this decision properly, in order to provide a survival benefit. Some years ago in the USA, the benefit of lung transplantation in children with cystic fibrosis was questioned.18 This was possibly linked to too early inclusion on the waiting list in contrast to the improvement in survival of children with cystic fibrosis due to advances in medical treatment.11 With the adoption of a severity assessment system for prioritizing patients on the waiting list (Lung Allocation Score), a real benefit of transplantation in adults with cystic fibrosis been shown in the USA19; this scoring system is only applicable in children over 12 years of age. In other countries, a real benefit of lung transplantation has been demonstrated in children with cystic fibrosis and severe lung disease.20

The indications for referring a child with cystic fibrosis for evaluation for lung transplant can be summarized in: frequent hospital admissions for intravenous antibiotic treatment, major limitation for attending school or carrying out normal activities, rapid decline or marked fluctuations in lung function, including an FEV1 <30%, recurrent pneumothorax or hemoptysis, hypoxemia and hypercapnia.16,17 It is recommended that children be included if their life expectancy is less than 2 years despite receiving full medical therapy and they have poor quality of life that is likely to improve with transplantation.11 Using this approach, widely adopted in Europe, most of those who receive a transplant will benefit, although it has the disadvantage that some patients may die on the waiting list or even without being included on it if their prognosis is not properly assessed.11

In children with diffuse parenchymal lung diseases, the most important thing is to assess the presence of moderate or severe functional impairment, need for mechanical ventilation or very high oxygen supplementation, lack of response to treatment, and taking into account the natural course of the disease.15 With some diseases, such as surfactant protein B deficiency, the child cannot survive without a transplant, while others may have a variable response to treatment, as in surfactant protein C deficiency.16

The prognosis in pulmonary hypertension has improved considerably with the new treatments available, so the following criteria are now recommended: children in functional class IV: place on the transplant list and begin medical treatment; if they improve, remove them from the waiting list. Children in functional class III: administer medical treatment; if they do not improve or worsen, place them on the waiting list. Children with bilateral pulmonary vein stenosis or alveolar capillary dysplasia would have to be included on the transplant list at an early stage, as they do not respond to other treatments.13,16

The nature of these indications means that lung transplantation in mechanically ventilated children is indicated more often than in adults. Infants on mechanical ventilation or children on long-term mechanical ventilation may be considered candidates for lung transplant. It has been shown that mechanically ventilated infants who have received transplants have the same survival post-transplant as non-ventilated older children, and better than ventilated older children.21 Invasive mechanical ventilation in children with cystic fibrosis is a risk factor for higher post-transplant morbidity and mortality, unlike non-invasive ventilation.22–24

Table 3 summarizes the criteria for referring children to lung transplant teams.

There are several situations in which lung transplantation may not be advised, some absolute and others relative,17 while some are specific to each centre (Table 4).

In patients with cystic fibrosis, Bulkholderia cepacia genomovar-3, Mycobacterium abscessus and multiresistant fungal infections (Schedosporium prolificans) constitute a contraindication in some centers.

Patients with cyanotic heart diseases in whom previous thoracotomies have been performed for palliative purposes have a very high risk of bleeding from chest wall collateral vessels, and should be assessed individually.

One of the current critical issues in pediatric lung transplantation, and pediatric transplants in general, is the fall in the number of young donors available, with the consequent increase in waiting list times. This is linked to the gradually decreasing number of donors as a result of road traffic accidents in the last 20 years, in parallel with the decrease in road fatalities, particularly after the introduction of new road traffic laws in Spain in 2005. While they represented 43% of donors in 1992, this figure fell to 5.7% of total donations in 2010.5

In our hospital, the median waiting time for children under 2 years old between the periods 1996–2005 and 2006–2011 increased moderately from 84 to 135 days, while for the 3–11 and 12–17 years age groups, it increased significantly, from 107 to 538 days and from 106.5 to 404.5 days, respectively.

In order to improve these figures, Pediatric Intensive Care Units must be extremely aware of the need to make the most of potential donors and to optimize their care, and strategies for using lungs from adult donors in children may be employed; it would also be advisable to explore the extension of non-heart-beating donor programs in pediatrics.8,25

Sequential double-lung transplant is typically carried out in children; this is compulsory in septic lung disease (cystic fibrosis) and is the procedure of choice in pulmonary hypertension. Single-lung transplantation is less indicated in children than in adults (only 1 out of 31 cases in the Spanish Lung Transplant Registry5). It can be performed in cases of non-septic parenchymal lung disease (pulmonary fibrosis, bronchiolitis obliterans, retransplantation), if the somatic growth is almost complete and the organ offered is of perfect size and quality. Heart-lung transplant is reserved for pulmonary vascular disease associated with uncorrectable congenital heart disease, and for cases in which there is left ventricular failure.

Unlike adults, most pediatric lung transplants are performed with CPB, as most children, due to their size, cannot tolerate single-lung ventilation. However, in adolescents and older children, it is sometimes possible to perform the transplant without CPB.2 Although it has been suggested that the use of this technique could be associated with a higher incidence of primary graft failure, in a large series comparing the frequency of primary graft dysfunction between transplants in adults and children, there were no differences in its incidence.26

Due to the difficulty in finding donors of a suitable size for children, there is greater flexibility in accepting size differences between the donor and recipient, and various techniques are performed to accommodate the lungs, including lobectomies (the middle lobe, lingula or lower lobes), non-anatomical resections, or using the lobes only. The upper or lower lobes can be used, but the upper lobes fit better in the thorax.27 Another strategy that has been used is to divide the left lung of an adult donor of suitable size, using the left lower lobe as a left lung and the left upper lobe as a right lung.27 There is experimental evidence in animal models that a “mature” lobe implanted in an immature recipient could grow by pneumocyte division.28

Living donor lobar lung transplantation requires 2 donors, extracting the lower lobe from each of them. This has significant morbidity for the donor and results similar to those of a deceased donor, so it is rarely used at present, except in Japan and Brazil and occasionally in some experienced centers in the USA.16

Post-transplant treatment and follow-up is similar to that in adult patients, although there are some major differences.

The authors declare that they do not have any conflict of interests.