Lung transplantation for pediatric pulmonary hypertension

Abstract

Lung and heart–lung transplantation are accepted therapies for the treatment of end-stage lung or cardiovascular disease in children for whom there are no medical or surgical treatment options. Worldwide, more than 200 children have undergone this procedure since 1986 and 1987, when respectively, the first pediatric heart–lung transplant and the first pediatric lung transplant procedures were performed. The issues that relate to surgical techniques as well as outcomes are distinctly unique for children compared to adults. End-stage pulmonary vascular disease due to primary pulmonary hypertension (PAH) is one of the primary indications for lung or heart–lung transplantation. Generally, for all pediatric lung transplant recipients, the outcomes are comparable to those of adult recipients, with a median survival of 4.3 years. As well, children experience a marked improvement in quality of life. Even though PAH is one of the leading indicators for lung or heart–lung transplantation in children, the survival outcomes for pediatric PAH lung transplant recipients are difficult to accurately calculate, given the very low total numbers of children who have undergone transplantation. Between January of 2000 and June of 2006, 138 children received lung transplantation worldwide. They account for less than 4% of all lung transplants performed since the inception of the procedure for adults in 1982. Adult PAH patients have decreased survival compared to other indicators. There is a higher mortality rate while on the lung waiting list, an increased 90-day mortality post-operatively, and lower expected survival to 5 years after transplant. The immune suppressants generally utilized consist of a triple drug regimen that includes a calcineurin inhibitor, a lymphocyte anti-proliferative agent, and corticosteroid. Until recently, centers varied widely in the specific protocols for drug doses and for treatment of the various complications that occur post-operatively, such as acute cellular rejection, humoral rejection, post transplant lymphoproliferative disorder (PTLD), and emergence of chronic allograft rejection, aka bronchiolitis obliterans syndrome (BOS). Although survival after pediatric lung and heart–lung transplantation has improved over the last decade, it is still well below that of heart and most other solid organ transplants. BOS is the single most important life-limiting complication of lung and heart–lung transplantation, yet the pathophysiology of BOS appears to be multifactorial and is poorly understood. To date, little advancement has been made in the prevention and treatment for BOS. Ongoing challenges remain to optimize organ allocation as well as treatment regimens. The pediatric lung transplant community is collaborating internationally, and has standardized treatment regimens across centers. In the future, this will permit multi-center studies to compare patient outcome measures head to head and illuminate the pathophysiology of immunological and other mechanisms that lead to graft failure and provide new therapeutic avenues.