Letter by Eberlein and Reed Regarding Article, “Transplantation for Idiopathic Pulmonary Arterial Hypertension: Improvement in the Lung Allocation Score Era”
To the Editor:
We read with great interest the article by Schaffer et al1 on transplantation for idiopathic pulmonary arterial hypertension (IPAH). A conclusion of the authors is that donor-to-recipient sex matching is associated with better survival. Furthermore, sex matching as a priority for IPAH patients with less acute disease is recommended. The accompanying editorial emphasizes that the findings regarding sex matching need to be evaluated in more detail.
An important detail unaccounted for by Schaffer et al1 is that sex is a major determinant of lung size.2 Lung size can be estimated by calculating the predicted total lung capacity (pTLC) from height and sex.2–5 Donor-to-recipient lung size mismatch can be estimated by the pTLCratio (pTLC donor:pTLC recipient). We have shown that the pTLCratio is associated with survival after lung transplantation.2–5 Specifically, a higher pTLC:ratio, suggestive of an oversized allograft, is associated with improved survival after lung transplantation.2–5 Furthermore, when lung size mismatch was accounted for, donor sex, recipient sex, or the interaction between the 2 was not independently associated with survival.2,4,5 More importantly, within the diagnosis of IPAH, the pTLCratio predicts survival.4 In a United Network for Organ Sharing database analysis of IPAH subjects, median survival after transplant was 831 days longer in the oversized cohort compared with the undersized cohort (P=0.006).4 In a multivariate model controlling for sex mismatch, recipient factors, acuity, donor factors, and transplant factors, oversizing continued to be associated with improved survival. An analysis by quartiles of pTLC:ratio supported a nonlinear, U-shaped association with survival, the lowest risk of death with moderate oversizing, whereas both undersizing and extreme oversizing showed an association with increased risk for mortality after transplant. After adjustment for lung size mismatch, sex was not independently associated with survival after transplant for IPAH.4
We believe that there is increasing evidence that donor-to-recipient sex mismatching is not independently associated with survival after lung transplantation, when the sex effect on lung size is accounted for. Thus, the recommendation that sex matching should be a priority for IPAH patients with less acute disease should be approached with caution, and further studies accounting for donor-to-recipient lung size mismatch are needed. In the United States, donors are matched to recipients via acceptable height ranges. This approach does not take the sex effect on lung size into consideration.2,5 However, a pTLC-based approach would make apparent the significant lung size mismatch that can occur with a donor-to-recipient sex mismatch. In our opinion, lung transplant recipients should be listed for acceptable donor pTLC ranges rather than donor height ranges, and we would recommend including the pTLCratio in the peritransplant risk assessment.
Michael Eberlein, MD, PhD
Division of Pulmonary, Critical Care and Occupational Medicine
University of Iowa Hospitals and Clinics
Iowa City, IA
Robert M. Reed, MD
Division of Pulmonary and Critical Care Medicine
University of Maryland
Dr Reed is funded in part by the Alpha-1 Antitrypsin Foundation/Chest Foundation as well as the Flight Attendant Medical Research Institute.
- © 2014 American Heart Association, Inc.