Characterization of Donor to Recipient Size Matching in Lung Transplantation

Original Article

Austin J Pulm Respir Med 2014;1(3): 1014.

Characterization of Donor to Recipient Size Matching in Lung Transplantation

Hisham Taher1, Robert M Reed2 and Michael Eberlein1*

1Division of Pulmonary, University of Iowa Hospitals and Clinics, Iowa

2Division of Pulmonary and Critical Care Medicine, University of Maryland Scholl of Medicine, Maryland

*Corresponding author: Michael Eberlein, Lung Transplant Program, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, C 33 GH, Iowa City, IA 52242

Received: June 01, 2014; Accepted: July 28, 2014; Published: Aug 04, 2014

Abstract

Rationale: Donor to recipient lung size matching is an important aspect of lung transplantation (LTx). Height is an important predictor of lung size. However gender affects lung size independent of height. The predicted total lung capacity (pTLC), as an estimate of lung size, can be calculated from regression equations based on gender and height.

Objective: To characterize the donor-recipient lung size matching based on the pTLC ratio (= pTLC donor/pTLC recipient), height and gender.

Methods: All adult patients in the United Network for Organ Sharing (UNOS) transplant registry who underwent first-time LTx between October 1989 and April 2010 were studied, and the pTLC ratio was calculated. Subjects were then grouped into pTLC ratio strata (stratum 1: pTLC ratio<0.8 “very undersized”; stratum 2: pTLC ratio 0.8-1.0 “undersized”; stratum 3: pTLC ratio 1.0-1.2 “oversized” and stratum 4: pTLC ratio>1.2 “very oversized”).

Results: The pTLC ratio was available for 17,779 of the 19,812 study patients (89.7%). The mean pTLC ratio was 1.07 ± 0.21 (range 0.4 – 2.0). The mean pTLC ratio progressively decreased by transplant era from 1.14 in 1989 to 1.04 in 2010 (p <0.0001). Subjects in “size matched” strata 2 and 3 were 83% and 93% gender matched. In the very undersized stratum 1 87% of patients had a female donor to male recipient gender-mismatch, whereas in the very oversized stratum 4 80% of patients had a male donor to female recipient gender-mismatch. In the group of subjects with restrictive lung disease the percentage the very undersized stratum 1 increased from 5.9% in the 1989- 1994 eras to 16.4% in the 2006-2010 eras.

Conclusion: Donor-recipient lung size matching is best estimated by donor to recipient pTLC ratio, as the important effect of gender on lung size is accounted for in this metric. The evolution towards lower pTLC ratio’s (more under sizing) over time, especially for restrictive lung diseases, is contrary to the growing evidence showing the outcome benefits of oversized allograft.

Keywords: Lung transplantation; Lung size matching; predicted total lung capacity

Introduction

Donor to recipient lung size matching is an important aspect of lung transplantation (LTx) [1-4]. However it remains controversial what the best parameter for the size matching decision is and if parameters of donor-recipient lung size matching have a relationship to outcomes after LTx. The 27th -30thinternational society of heart and lung transplantation (ISHLT) registry report showed that donor to recipient height differences correlated with the risk of death at 1 year: the taller the donor in relation to the recipient, the lower the hazard ratio for one year mortality [5,6]. Worse survival after a female-donor to male recipient LTx has been reported in several studies [7,8]. In the United States potential recipients for lung transplantation are listed with acceptable donor height ranges [2]. Height is an important predictor of lung size [9]. However gender affects lung size independent of height [9]. The predicted total lung capacity (pTLC), as an estimate of lung size, can be calculated from regression equations based on gender and height [9]. Donor-recipient lung size matching can be estimated by donor to recipient pTLC ratio [3,4,10-18]. A study of bilateral lung transplant recipients from three transplant centers reported the association of a higher pTLC ratio, suggestive of oversized allograft with improved survival [16]. Furthermore an analysis of the Scientific Registry of Transplant Recipients (SRTR) database demonstrated an association between undersized allograft and increased mortality in the first year post-transplant [3]. The transplant indication can affect the lung size matching decision [1,3,12,16]. There is a general preference toward over sizing in chronic obstructive pulmonary disease (COPD) [1]. Whereas, for idiopathic pulmonary fibrosis (IPF) there is a general preference to undersize [1]. However in the SRTR database analysis there was no interaction between the pTLC ratio and lung disease diagnosis cluster (Lung allocation score groups A–D) on survival and the pTLC ratio was an independent predictor of 1 year mortality [3]. There was an interaction between the lung allocation score (a parameter of recipient acuity) and the pTLC ratio. The impact of pTLC ratio on 1 year mortality increased as the lung allocation score (i.e. acuity) increased [3].

The aim of this report is to characterize donor to recipient lung size matching based on the pTLC ratio, height, and gender and transplant indication using Organ Procurement and Transplantation Organization (OPTN) Standard Transplant Analysis and Research (STAR) files of the thoracic organ transplant registry.

Data Source

This study was approved by the Institutional Review Board at the Johns Hopkins Hospital and at the University of Iowa Hospitals and Clinics. STAR files with follow-up were provided by the OPTN. Data are compiled from individual centers and entered by trained data entry personnel using an electronic system with built-in data validation processes that cross-reference multiple sources. The data set comprises a prospectively collected open cohort of U.S. LTx patients (10/1989 through 4/2010) with follow-up through July 2010.

Study Design

This cohort study examined adult (aged ≥18 years) primary LTx patients from October 1989 to April 2010. Estimates of lung and thorax size were calculated from sex and height, as the predicted total lung capacity (pTLC) [9].

-pTLC for Male = 7.99 x [Height in meter] - 7.08.

-pTLC for Female= 6.60 x [Height in meter] - 5.79.

The size of donor lungs was compared to the size of a recipient’s thorax by calculating the ratio of the donor’s pTLC to the recipient’s pTLC (pTLC ratio) [3,4,10-18]. Patients with missing information to calculate the pTCL ratio were excluded. Patients with height recordings below 100 cm, or with pTLC ratios <0.4 or >2.0 were excluded, with the concern that these likely represented a data entry error. Based on clinical size matching considerations, patients were then grouped into pTLC ratio strata (stratum 1: pTLC ratio<0.8 “very undersized”; stratum 2: pTLC ratio 0.8-1.0 “undersized”; stratum 3: pTLC ratio 1.0-1.2 “oversized” and stratum 4: pTLC ratio>1.2 “very oversized”).

Statistical Analysis

Baseline characteristics were compared among pTLC ratio strata by one-way analysis of variance (continuous variables) and chi-square tests (categoric variables). For significant associations, pair-wise comparisons were performed by using the Tukey-Kramer method for continuous variables or by univariate logistic regression for categoric variables.

For all analyses, p<0.05 (2-tailed) was significant. Means are presented with standard deviations, medians with interquartile range (IQR), and hazard ratios (HR) with 95% confidence intervals (CI). Statistical analysis was performed using STATA 11 SE software (Stata Corp-LP, College Station, TX).

Results

Study population

From 1989 to 2010, 19,812 adult patients underwent first time LTx. The pTLC ratio was available for 17,779 patients (89.7%) and these constituted the study population. The mean pTLC ratio progressively decreased by transplant era from 1.14 in 1989 to 1.04 in 2010 (p <0.0001).Within diagnosis there was a decrease in the mean pTLC ratio by era in idiopathic pulmonary fibrosis (IPF), primary pulmonary hypertension (PPH) and “Other” indications, whereas the mean pTLC ratio of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients did not change significantly, Figure 1.