Impact of lung function interpretation approach on pediatric bronchiolitis obliterans syndrome diagnosis after lung transplantation

Abstract

Background: The diagnostic criteria for bronchiolitis obliterans syndrome (BOS) are predominantly adult-focused. The relationship between application and impact of reference equation choice on pediatric baseline lung function achieved and subsequent BOS diagnosis remains unclear.

Methods: Lung function spirometry data (FEV(1), FVC and FEF(25-75)) from pediatric subjects transplanted at the Great Ormond Street Hospital over a 10-year period were collated. Baseline values achieved after lung transplantation and BOS rates were examined. Raw values were compared with 2 different reference equations (the "Brompton" and modern collated "All-age" equations). The impact of FEF(25-75) baseline definition was investigated.

Results: Fifty subjects were included, 17 males and 33 females, transplanted at a median (range) age of 14.0 years (3.2 to 17.3 years, 83% >10 years old), and followed for 1,028 (388 to 2,613) days post-transplantation. Raw values underestimated baseline lung function attainment for all indices. Magnitude of baseline lung function was affected by reference equation choice. Mean FEV(1) values were: Brompton 97.9% (SD 20.3%) and All-age 86.3% (SD 15.4%) of predicted (p < 0.0001). BOS 0p incidence was significantly higher for All-age predicted than for raw values (64% and 40%, respectively, p = 0.027). Modification of FEF(25-75) baseline (to either FEV(1) or FVC baseline) led to a reduction in BOS 0p detection (p < 0.01).

Conclusions: Modern collated reference equations should be used for lung function monitoring in pediatric subjects after lung transplantation. Standardization of FEF(25-75) baseline definition is urgently required. These data question the utility of the FEF(25-75) criterion as an early marker of BOS 0p in pediatric subjects.

Keywords: bronchiolitis obliterans syndrome; lung function; monitoring; pediatric; reference equations; spirometry.