Obesity and underweight are associated with an increased risk of death after lung transplantation

Abstract

Rationale: Obesity is considered a relative contraindication to lung transplantation, based on studies that have not accounted for key confounders. Little is known about the risk of death for underweight candidates after transplantation.

Objectives: To examine the associations of pretransplant obesity and underweight with the risk of death after lung transplantation.

Methods: We examined 5,978 adults with cystic fibrosis, chronic obstructive pulmonary disease, and diffuse parenchymal lung disease who underwent lung transplantation in the United States between 1995 and 2003. We used Cox models and generalized additive models to examine the association between pretransplant body mass index and the risk of death after lung transplantation with adjustment for donor and recipient factors.

Measurements and main results: The median follow-up time was 4.2 years. Compared with normal weight recipients, the multivariable-adjusted rates of death were 15% higher for underweight recipients (95% confidence interval, 3 to 28%), 15% higher for overweight recipients (95% confidence interval, 6 to 26%), and 22% higher for obese recipients (95% confidence interval, 8 to 39%). These relationships persisted when stratified by diagnosis. The multivariable-adjusted population attributable fraction was 12% at 1 year and 8% at 5 years.

Conclusions: Both obesity and underweight are independent risk factors for death after lung transplantation, contributing to up to 12% of deaths in the first year after transplantation. Primary care providers and pulmonologists should promote a healthy weight for patients with lung disease long before transplantation is considered.

Figure 1.

Study participants.

Figure 2.

Multivariable-adjusted survival curves for underweight, normal weight, overweight, and obese lung transplant recipients. Survival estimates are adjusted for the covariates in model 4 listed in the footnote to Table 2. Bottom: Numbers indicate the number of surviving lung transplant recipients at each time point.

Figure 3.

Continuous relationships of body mass index and the risk of death (A) at 1 year and (B) at 5 years conditional on 1-year survival after lung transplantation. Thick dotted lines = smoothed regression lines adjusted for the model 4 covariates listed in the footnote to Table 2. Thin solid lines = 95% confidence intervals. In (A), both nonlinear (P = 0.02) and linear (P = 0.02) relationships were statistically significant. In (B), the nonlinear (P = 0.04), but not the linear (P = 0.35), relationship was statistically significant. The significant P values for the smoothed (nonlinear) curves suggest that the relationship between body mass index and the risk of death after lung transplantation is nonlinear, with higher early and late mortality rates for both underweight and obese recipients. The wide confidence intervals at the extremes of body mass index are due to smaller numbers of transplant recipients with these values.

Figure 4.

Multivariate-adjusted survival curves for underweight, normal weight, overweight, and obese lung transplant recipients with (A) cystic fibrosis, (B) chronic obstructive pulmonary disease, (C) and diffuse parenchymal lung disease. Survival estimates are adjusted for the covariates listed in the footnote to Table 2 (model 4). Bottom: Numbers indicate the number of surviving lung transplant recipients at each time point.