Body composition and mortality after adult lung transplantation in the United States - PubMed (original) (raw)

. 2014 Nov 1;190(9):1012-21.

doi: 10.1164/rccm.201405-0973OC.

Eric R Peterson, Mark E Snyder, Patricia P Katz, Jeffrey A Golden, Frank D'Ovidio, Matthew Bacchetta, Joshua R Sonett, Jasleen Kukreja, Lori Shah, Hilary Robbins, Kristin Van Horn, Rupal J Shah, Joshua M Diamond, Nancy Wickersham, Li Sun, Steven Hays, Selim M Arcasoy, Scott M Palmer, Lorraine B Ware, Jason D Christie, David J Lederer

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Body composition and mortality after adult lung transplantation in the United States

Jonathan P Singer et al. Am J Respir Crit Care Med. 2014.

Abstract

Rationale: Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed before implementation of the lung allocation score (LAS)-based organ allocation system in the United States Objectives: To determine the associations of body mass index (BMI) and plasma leptin levels with survival after lung transplantation.

Methods: We used multivariable-adjusted regression models to examine associations between BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual X-ray absorptiometry in 142 adult lung transplant candidates.

Measurements and main results: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9), and class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI < 18.5) was associated with a 35% increased rate of death (95% confidence interval, 10-66%). Class II-III obesity (BMI ≥ 35 kg/m(2)) was associated with a nearly twofold increase in mortality (hazard ratio, 1.9; 95% confidence interval, 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (P for interaction = 0.03). A BMI greater than or equal to 30 kg/m(2) was 26% sensitive and 97% specific for total body fat-defined obesity.

Conclusions: A BMI of 30.0-34.9 kg/m(2) is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps because of its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI greater than or equal to 30 kg/m(2) may no longer contraindicate lung transplantation.

Keywords: adiposity; biomarker; leptin; obesity; sarcopenia.

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Figures

Figure 1.

Figure 1.

Study flow for (A) Organ Procurement and Transplantation Network, (B) Lung Transplant Body Composition, and (C) Lung Transplant Outcomes Group cohorts. DXA = dual X-ray absorptiometry.

Figure 2.

Figure 2.

(A) Continuous association between pretransplant body mass index (BMI) and the risk of death 1 year after lung transplantation, and predicted 1-year mortality curves by BMI category (B) overall and for subgroups with (C) chronic obstructive pulmonary disease and (D) interstitial lung disease. In_A_, the thick dotted line = smoothed regression line adjusted for age, diagnosis, lung allocation score, transplant type (single or bilateral lung), ischemic time, mechanical ventilation at the time of transplant, and transplant center. Thin dashed lines_= 95% confidence intervals. The vertical hash marks in the rug plot at the bottom represent unique study participants. The_P value for linearity is 0.02, supporting a nonlinear association between body mass index and risk of mortality at 1 year. The_P_ value for the linear association is 0.80. The wide confidence intervals at the extremes of BMI are caused by fewer transplant recipients with these values. In B–D, predicted survival estimates with covariates listed in the footnote to Table 1 set to their mean values (Model 3). Body mass index categories: underweight (BMI < 18.5), normal (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese class I (BMI 30.0–34.9), obese class II–III (BMI ≥ 35.0).

Figure 3.

Figure 3.

Scatterplots of (A) pretransplant body mass index (BMI) and percent body fat, (B) leptin and pretransplant BMI, and (C) leptin and pretransplant percent body fat in Lung Transplant Body Composition study participants. In A,vertical lines denote World Health Organization BMI categories: underweight (BMI < 18.5), normal (BMI 18.50–24.99), overweight (BMI 25.00–29.99), and obese (BMI ≥ 30.00).Horizontal lines are sex-specific thresholds for obesity defined by whole-body dual X-ray absorptiometry (DXA) (24). Table below: prevalence of obesity and mean (standard deviation) percent body fat within each BMI category. In_B_ and C, correlation coefficients are (B) r = 0.62 for leptin and BMI, and (C) r = 0.82 for leptin and percent body fat measured by whole-body DXA. TBF = total body fat.

Figure 4.

Figure 4.

Continuous associations between pretransplant plasma leptin level and the predicted risk of death at 1 year after transplantation in the Lung Transplant Outcomes Group Cohort. Green = lung transplant recipients not exposed to cardiopulmonary bypass (CPB) during transplant surgery.Blue = lung transplant recipients exposed to CPB during transplant surgery. Thick dotted lines = smoothed regression lines in 599 adult lung transplant recipients adjusted for body mass index category, age, recipient sex, lung allocation score, diagnosis (chronic obstructive pulmonary disease includes α1-antitrypsin disease), donor sex, donor smoking history, ischemic time, transplant type (single vs. bilateral), mechanical ventilation, transplant year, and transplant center. Thin dashed lines = 95% confidence bands. Leptin levels were natural log transformed. CPB-stratified models are presented (P for interaction = 0.03). The _P_values for linearity are 0.15 for CPB users and 0.33 for nonusers, suggesting a lack of evidence that the associations are nonlinear. The _P_values for the association between leptin and mortality are 0.39 for CPB users and 0.03 for nonusers. These results suggest higher leptin levels are associated with an increased risk of death after lung transplantation among those who did not undergo CPB during transplant surgery.

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