Lung transplantation from a deceased donor into an Asian cystic fibrosis patient

Abstract

Lung transplantation (LTx) has become an established treatment for end-stage lung failure refractory to medical management. The major limiting factor for the number of LTx procedures performed is the shortage of available donor organs. This results in longer waiting times for listed patients, with substantially increased risk of dying before transplantation, especially in Asia. For life-threatening, end-stage lung disease, such as cystic fibrosis (CF) with severe pulmonary exacerbations and respiratory failure, most patients die while waiting for suitable organs. Because of the severe organ shortage from deceased donors and the rare incidence of CF among Asians, only one 6-year-old CF patient has received a lobar LTx from a living donor.1,2 A 20-year-old man with diffuse bronchiectasis and chronic respiratory tract infection with Pseudomonas aeruginosa was referred to us for LTx. His FVC was 1.77 L (35% of predicted) and his FEV1 was 0.78 L (18% of predicted). The diagnosis of CF with established pulmonary arterial hypertension (PAH) was based on clinical characteristics, radiographic and cardiac catheterization findings, and the identification of pathological mutations affecting the CFTR gene, a homozygous mutation in exon 12 (1898 + 5G > T). After being on the waiting list for more than 6 months, the patient was hospitalized and mechanically ventilated due to respiratory failure and acute exacerbation of Pseudomonas pneumonia. Five days later, the patient underwent bilateral sequential LTx (BSLTx) with extracorporeal membrane oxygenation (ECMO) support. The postoperative course was complicated by localized impaired anastamotic healing, which improved over 3 weeks. The patient was discharged 2 months after LTx with an FEV1 of 3.15 L (71% of predicted). To the best of our knowledge, this is the first deceased donor BSLTx for an Asian CF patient. In the published English literature, there are only five Taiwanese CF patients (including our patient) whose CF diagnosis was confirmed by definitive molecular CFTR mutation scanning. The 1898 + 5G>T mutation, which causes skipping of exon 12 in the CFTR, was found in four of the five patients (80%).3–5 These observations implied that the incidence of CF in Taiwan was so rare and the prevalence of 1898 + 5G>T mutation in Taiwanese CF patients may be actually higher than estimated by Zielenski et al. 13 years ago.6 Madiha and colleagues reported the 1-year mortality rate was 47.8% in the group of CF patients requiring treatment in the ICU, whereas it was only 8.7% in those whose pulmonary exacerbation was managed in the pulmonary department.7 In the study by Sood and colleagues, the 1-year mortality rate was nearly 60% (25 of 42) among CF patients hospitalized in the ICU for pulmonary exacerbations and most of the survivors (14 of 17) benefited from LTx.8 These two recent studies clearly demonstrated that pulmonary exacerbations among patients with CF significantly affected mortality during the period after hospitalization in an ICU. Urgent LTx could provide a life-saving therapeutic option among these critically ill patients. The pathophysiology of PAH in CF patients results from increasing right heart afterload due to pulmonary dynamic hyperinflation and loss of pulmonary vasculature due to destructive disease. Without cardiopulmonary (CPB) bypass support, achieving adequate ventilation during LTx is often difficult in end-stage CF patients with PAH. ECMO life support is well established in our centre and provided adequate cardiopulmonary support during BSLTx.9–11 Furthermore, due to use of heparin-bound cannulas, there is no need for systemic heparinization in the ECMO circuit. Thus, ECMO eliminates bleeding complications during the LTx procedure in patients with severe intrapleural adhesions better than CPB. We thank the Bureau of Health Promotion in Taiwan and the Taiwan Foundation for Rare Disorders for providing financial support for the DNA analysis, which was performing by Canterbury Health Laboratories in Christchurch, New Zealand.