Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients

Abstract

Rationale: Despite the importance of bronchiolitis obliterans syndrome (BOS) in lung transplantation, little is known regarding the factors that influence survival after the onset of this condition, particularly among bilateral transplant recipients.

Objectives: To identify factors that influence survival after the onset of BOS among bilateral lung transplant recipients.

Methods: The effect of demographic or clinical factors, occurring before BOS, upon survival after the onset of BOS was studied in 95 bilateral lung transplant recipient using Cox proportional hazards models.

Measurements and main results: Although many factors, including prior acute rejection or rejection treatments, were not associated with survival after BOS, BOS onset within 2 years of transplantation (early-onset BOS), or BOS onset grade of 2 or 3 (high-grade onset) were predictive of significantly worse survival (early onset P = 0.04; hazard ratio, 1.84; 95% confidence interval, 1.03-3.29; high-grade onset P = 0.003; hazard ratio, 2.40; 95% confidence interval, 1.34-4.32). The effects of both early onset and high-grade onset on survival persisted in multivariable analysis and after adjustment for concurrent treatments. Results suggested an interaction might exist between early onset and high-grade onset. In particular, high-grade onset of BOS, regardless of its timing after transplant, is associated with a very poor prognosis.

Conclusions: The course of BOS after bilateral lung transplantation is variable. Distinct patterns of survival after BOS are evident and related to timing or severity of onset. Further characterization of these subgroups should provide a more rational basis from which to design, stratify, and assess response in future BOS treatment trials.

Figures

Figure 1.

Survival after the onset of bronchiolitis obliterans syndrome (BOS) among 95 bilateral lung transplant recipients. Kaplan-Meier survival estimates at 1, 3, and 5 years after the onset of BOS were 74%, 46%, and 26%, respectively. Median survival was limited to 2.5 years (IQR, 0.8–5.5 yr).

Figure 2.

The impact of time to bronchiolitis obliterans syndrome (BOS) onset on survival after the onset of BOS among 95 bilateral lung transplant recipients. Early-onset BOS (onset within 2 yr of lung transplant), occurring in 34% (32/95) of patients, was associated with significantly increased mortality as compared with late onset (P = 0.04; hazard ratio, 1.84; 95% CI, 1.03–3.29). Four-year Kaplan-Meier survival estimates after BOS for the early-onset group were 24% in contrast with 32% in the late-onset group; P = 0.04.

Figure 3.

The impact of bronchiolitis obliterans syndrome (BOS) onset grade on survival after the onset of BOS among 95 bilateral lung transplant recipients. High-grade onset BOS (initial BOS grades 2 or 3), occurring in 26% (25/95) of patients, was associated with significantly increased mortality as compared with grade 1 onset (P = 0.0034; HR, 2.40; 95% CI, 1.34–4.32). Four-year Kaplan-Meier survival estimates after BOS for high-grade onset versus grade 1 onset were 11% and 45% respectively; P = 0.003.

Figure 4.

Distinct patterns of survival after bronchiolitis obliterans syndrome (BOS) among 95 bilateral lung transplant recipients: survival by high-grade BOS onset, survival by grade 1 and early onset, and survival by grade 1 and late onset. Among the patients with BOS, 13% (12/95) presented in high-grade and early onset, 14% (13/95) presented in high-grade and late onset, 21% (20/95) presented in grade 1 and early onset, and 52% (50/95) presented in grade 1 and late onset. Overall survival was significantly different among these four groups (P = 0.007).